Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of the maternal allele of the UBE3A gene, which encodes a protein essential for ubiquitin-mediated protein degradation. AS mouse models exhibit elevated lactate and acetate levels and increased Ldha expression in fibroblasts. We hypothesize that maternal UBE3A loss alters the protein levels of LDHA, LDHB, MCT2, and MCT1, contributing to elevated brain lactate levels. Western blot analysis of the cerebellum from adult Ube3am-/p+ AS and wild-type mice reveals significant sex- and genotype-specific differences in LDHB expression. Loss of Ube3a alters the expression of LDHB in the cerebellum.
","acknowledgements":"","authors":[{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico"],"departments":["Biomedical Sciences "],"credit":["conceptualization","methodology","formalAnalysis","investigation","project","validation","writing_originalDraft","writing_reviewEditing"],"email":"mramosrivera5@pucpr.edu","firstName":"Miriam Arlene","lastName":"Ramos Rivera","submittingAuthor":true,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":null},{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, PR"],"departments":["Natural Sciences"],"credit":["project","resources","supervision","writing_reviewEditing"],"email":"ceidy_torres@pucpr.edu","firstName":"Ceidy","lastName":"Torres-Ortiz","submittingAuthor":false,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":null}],"awards":[],"conflictsOfInterest":null,"dataTable":null,"extendedData":[],"funding":"\n\n\n\nThe research was supported by funding provided to Dr. Ceidy Torres Laboratory by the Scientific Research\nCenter of the Pontifical Catholic University of Puerto Rico.\n\n\n\n","image":{"url":"https://portal.micropublication.org/uploads/9daecea8559f9ac726180df1dafed57d.png"},"imageCaption":"Note: Graphs a, b, d, and f show protein expression of LDHA, LDHB, MCT2, and MCT1 in the cerebellum, while k, l, m, and n show these in the hippocampus. Student's T-Test (N=20) found a significant difference in LDHB fold change between AS and WT (P=0.0113). (c) shows LDHB expression in the cerebellum (36 kDa) with β-Actin at 45 kDa. Graphs f, g, i, j, o, p, and q compare gender and genotype using Two-Way ANOVA; no significant differences in (a, d, e, f, j, o, p, q, r). (g) reports a significant LDHB difference in cerebellum males (P=0.0128, N=10 per group). (h) shows antibody bands on the cerebellum membrane, at 45 kDa for β-Actin and 37 kDa for LDHB; first two columns: males, last two: females. Created in BioRender.com.
","imageTitle":"LDHA, LDHB, MCT2, and MCT1 Protein Expression in the Cerebellum and Hippocampus
","methods":"\n\n\n\nWestern Blot\nAnalysis: \n\n\n\n\n\nThe\nhippocampus and cerebellum frozen tissues were homogenized in 300 μL RIPA\nbuffer (50 mM Tris-HCl, 150 mM NaCl, 1% NP-40, 0.5% sodium deoxycholate, 0.1%\nSDS) supplemented with protease and phosphatase inhibitors (Pierce TM Protease and Phosphatase Inhibitor Mini Tablets, Thermo Scientific). The protein concentration was determined\nusing the Qubit Protein BR Assay Kit (Invitrogen, now\nThermo Fisher Scientific) as per the manufacturer’s\ninstructions. The protein was denatured with 5x Laemmli sample buffer (10%\nsodium dodecyl sulfate, 25% 2-mercaptoethanol, 30% glycerol, 0.05% bromophenol\nblue, 292 mM Tris HCl pH 6.8) at 95°C for 10 minutes before loading onto a 4-15%\ngradient polyacrylamide gel (BIO-RAD Criterion™ TGX™ Precast Gels) and\nelectrophoresing at 80V in 1x running buffer (25 mM Tris, 192 mM glycine, 0,1%\nSDS, pH 8.3) for 1.5 hr. 10 µg was loaded to visualize the expression of LDHA,\nLDHB, MTC1 and MCT2. The proteins were\ntransferred to a 0.2 µm PVDF membrane at 25V for 7 minutes in 1x transfer\nbuffer (Trans-Blot Turbo 5x Transfer Buffer, BIO-RAD) using the Trans-Blot Turbo system (BIO-RAD). The membranes\nwere blocked with 5% bovine serum albumin (BSA) in 50 mL of TBST for 1 h at\nroom temperature. Primary antibodies (Table 1) were diluted in TBST and\nincubated overnight at 4 °C on a shaker at 60 rpm. After incubation, the\nmembranes were washed three times with 10 mL TBST for 10 min each. Secondary\nantibodies (Table 1) were diluted in TBST and incubated for 1 h at room\ntemperature on the shaker. Protein detection was performed using the\nSuperSignal™ West Pico Plus Chemiluminescent Substrate (Thermo Fisher\nScientific). Equal volumes of enhancer solution and stable peroxide solution\nwere applied to the membrane and incubated on a shaker at 60 rpm for 5 min, after\nwhich the membrane was imaged. \n\n\n\n\n\n \n\n\n\n\n\nStatistical\nanalysis: The membrane images were analyzed\nusing ImageJ-win 64 to measure the intensity of the antibody bands. Then, the\ndata was normalized by dividing the band of interest by the band of the\nhousekeeping gene, β-Actin. Next, we averaged the normalized expression of the\nWT group (WT mean). Finally, we divided the normalized expression values for\nthe WT and AS groups by the WT mean to obtain fold changes. The fold-change\ndata were analyzed using a Student’s t-test to compare WT and AS across the\ndifferent tissues. A two-way analysis of variance (ANOVA) was used to compare\ngenotype and sex-specific differences. \n\n\n\n","reagents":"STRAIN | GENOTYPE | AVAILABLE FROM | |
Ube3am-/p+ (AS) | C57BL/6J | The Jackson Laboratory | |
Ube3am+/p+ (WT) | C57BL/6J | The Jackson Laboratory | |
ANTIBODY | DILUTION | ANIMAL AND CLONALITY | AVAILABLE FROM |
anti-Lactate dehydrogenase A | 5:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
anti-Lactate dehydrogenase B | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Bethyl Laboratories |
anti-Monocarboxylate Transporter 2 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | EMD Millipore Corp |
anti-Monocarboxylate Transporter 1 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Thermo Fisher Scientific |
anti-Beta Actin | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
Goat anti-rabbit IgG(H+L), horseradish peroxidase conjugate | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Invitrogen by Thermo Fisher Scientific |
Bird L. 2014. Angelman syndrome: review of clinical and molecular aspects. The Application of Clinical Genetics : 93.
","pubmedId":"","doi":"10.2147/TACG.S57386 "},{"reference":"Dagli AI, Mathews J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2021 Apr 22]. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1144/
","pubmedId":"","doi":""},{"reference":"Leader G, Gilligan R, Whelan S, Coyne R, Caher A, White K, et al., Mannion. 2022. Relationships between challenging behavior and gastrointestinal symptoms, sleep problems, and internalizing and externalizing symptoms in children and adolescents with Angelman syndrome. Research in Developmental Disabilities 128: 104293.
","pubmedId":"","doi":"10.1016/j.ridd.2022.104293"},{"reference":"Simchi L, Panov J, Morsy O, Feuermann Y, Kaphzan H. 2020. Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation. Journal of Clinical Medicine 9: 1573.
","pubmedId":"","doi":"10.3390/jcm9051573"},{"reference":"Gupta PK, Barak S, Feuermann Y, Goobes G, Kaphzan H. 2024. 1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. Molecular Autism 15: 10.1186/s13229-024-00608-2.
","pubmedId":"","doi":"10.1186/s13229-024-00608-2"},{"reference":"Kim Y, Dube SE, Park CB. 2025. Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis. The Korean Journal of Physiology & Pharmacology 29: 1-8.
","pubmedId":"","doi":"10.4196/kjpp.24.388"},{"reference":"Medel, V., Crossley, N., Gajardo, I., Muller, E., Barros, L.F., Shine, J.M., & Sierralta, J. (2022). Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function. Proceedings of the National Academy of Sciences of the United States of America, 119 (33). Article 2204619119. https://doi.org/10.1073%2Fpnas.2204619119
","pubmedId":"","doi":"10.1073%2Fpnas.2204619119"},{"reference":"Liu Y, Beyer A, Aebersold R. 2016. On the Dependency of Cellular Protein Levels on mRNA Abundance. Cell 165: 535-550.
","pubmedId":"","doi":"10.1016/j.cell.2016.03.014"},{"reference":"Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. 2011. Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation. Cell 144: 810-823.
","pubmedId":"","doi":"10.1016/j.cell.2011.02.018"},{"reference":"Lu WT, Sun SQ, Li Y, Xu SY, Gan SW, Xu J, et al., Huang. 2018. Curcumin Ameliorates Memory Deficits by Enhancing Lactate Content and MCT2 Expression in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease. The Anatomical Record 302: 332-338.
","pubmedId":"","doi":"10.1002/ar.23969"},{"reference":"Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., et al., Yu, T. (2022). Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy, 7 (1), 305. Article 36050306. https://doi.org/10.1038%2Fs41392-022-01151-3
","pubmedId":"","doi":"10.1038%2Fs41392-022-01151-3"},{"reference":"Wang J, Cui Y, Yu Z, Wang W, Cheng X, Ji W, et al., Yang. 2019. Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis. Cell Stem Cell 25: 754-767.e9.
","pubmedId":"","doi":"10.1016/j.stem.2019.09.009 "},{"reference":"Hoshino D, Setogawa S, Kitaoka Y, Masuda H, Tamura Y, Hatta H, Yanagihara D. 2016. Exercise-induced expression of monocarboxylate transporter 2 in the cerebellum and its contribution to motor performance. Neuroscience Letters 633: 1-6.
","pubmedId":"","doi":"10.1016/j.neulet.2016.09.012"},{"reference":"Pierre K, Pellerin L. 2005. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. Journal of Neurochemistry 94: 1-14.
","pubmedId":"","doi":"10.1111/j.1471-4159.2005.03168.x"},{"reference":"Heck DH, Zhao Y, Roy S, LeDoux MS, Reiter LT. 2008. Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors. Human Molecular Genetics 17: 2181-2189.
","pubmedId":"","doi":"10.1093/hmg/ddn117"},{"reference":"Sun J, Liu Y, Moreno S, Baudry M, Bi X. 2015. Imbalanced Mechanistic Target of Rapamycin C1 and C2 Activity in the Cerebellum of Angelman Syndrome Mice Impairs Motor Function. The Journal of Neuroscience 35: 4706-4718.
","pubmedId":"","doi":"10.1523/JNEUROSCI.4276-14.2015"}],"title":"Lactate Dehydrogenase B Expression in Cerebellum of Adult Ube3a m-/p+ Mice
","reviews":[{"reviewer":{"displayName":"Tsui-Fen Chou"},"openAcknowledgement":false,"status":{"submitted":true}}],"curatorReviews":[]},{"id":"4c44e246-5d23-419b-b301-d85db15b5c31","decision":"revise","abstract":"Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of the maternal allele of the UBE3A gene, which encodes a protein essential for ubiquitin-mediated protein degradation. AS mouse models exhibit elevated lactate and acetate levels and increased Ldha expression in fibroblasts. We hypothesize that maternal UBE3A loss alters the protein levels of LDHA, LDHB, MCT2, and MCT1, contributing to elevated brain lactate levels. Western blot analysis of the cerebellum from adult Ube3am-/p+ AS and wild-type mice reveals significant sex- and genotype-specific differences in LDHB expression. Loss of Ube3a alters the expression of LDHB in the cerebellum.
","acknowledgements":"","authors":[{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico"],"departments":["Biomedical Sciences "],"credit":["conceptualization","methodology","formalAnalysis","investigation","project","validation","writing_originalDraft","writing_reviewEditing"],"email":"mramosrivera5@pucpr.edu","firstName":"Miriam Arlene","lastName":"Ramos Rivera","submittingAuthor":true,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":null},{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, PR"],"departments":["Natural Sciences"],"credit":["project","resources","supervision","writing_reviewEditing"],"email":"ceidy_torres@pucpr.edu","firstName":"Ceidy","lastName":"Torres-Ortiz","submittingAuthor":false,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":null}],"awards":[],"conflictsOfInterest":"The authors declare that there are no conflicts of interest present.
","dataTable":null,"extendedData":[{"description":"Western Blot images for each antibody for the hippocampus and cerebellum. ","doi":null,"resourceType":"Image","name":"Western Blot Images.png","url":"https://portal.micropublication.org/uploads/e69bade8c884ca38f29e3e7fbfe247b2.png"}],"funding":"\n\n\n\nThe research was supported by funding provided to Dr. Ceidy Torres Laboratory by the Scientific Research\nCenter of the Pontifical Catholic University of Puerto Rico.\n\n\n\n","image":{"url":"https://portal.micropublication.org/uploads/9daecea8559f9ac726180df1dafed57d.png"},"imageCaption":"Note: Graphs a, b, d, and f show protein expression of LDHA, LDHB, MCT2, and MCT1 in the cerebellum, while k, l, m, and n show these in the hippocampus. Student's T-Test (N=20) found a significant difference in LDHB fold change between AS and WT (P=0.0113). (c) shows LDHB expression in the cerebellum (36 kDa) with β-Actin at 45 kDa. Graphs f, g, i, j, o, p, and q compare gender and genotype using Two-Way ANOVA; no significant differences in (a, d, e, f, j, o, p, q, r). (g) reports a significant LDHB difference in cerebellum males (P=0.0128, N=10 per group). (h) shows antibody bands on the cerebellum membrane, at 45 kDa for β-Actin and 36 kDa for LDHB; first two columns: males, last two: females. Created in BioRender.com.
","imageTitle":"LDHA, LDHB, MCT2, and MCT1 Protein Expression in the Cerebellum and Hippocampus
","methods":"\n\n\n\nWestern Blot\nAnalysis: \n\n\n\n\n\nThe\nhippocampus and cerebellum frozen tissues were homogenized in 300 μL RIPA\nbuffer (50 mM Tris-HCl, 150 mM NaCl, 1% NP-40, 0.5% sodium deoxycholate, 0.1%\nSDS) supplemented with protease and phosphatase inhibitors (Pierce TM Protease and Phosphatase Inhibitor Mini Tablets, Thermo Scientific). The protein concentration was determined\nusing the Qubit Protein BR Assay Kit (Invitrogen, now\nThermo Fisher Scientific) as per the manufacturer’s\ninstructions. The protein was denatured with 5x Laemmli sample buffer (10%\nsodium dodecyl sulfate, 25% 2-mercaptoethanol, 30% glycerol, 0.05% bromophenol\nblue, 292 mM Tris HCl pH 6.8) at 95°C for 10 minutes before loading onto a 4-15%\ngradient polyacrylamide gel (BIO-RAD Criterion™ TGX™ Precast Gels) and\nelectrophoresing at 80V in 1x running buffer (25 mM Tris, 192 mM glycine, 0,1%\nSDS, pH 8.3) for 1.5 hr. 10 µg was loaded to visualize the expression of LDHA,\nLDHB, MTC1 and MCT2. The proteins were\ntransferred to a 0.2 µm PVDF membrane at 25V for 7 minutes in 1x transfer\nbuffer (Trans-Blot Turbo 5x Transfer Buffer, BIO-RAD) using the Trans-Blot Turbo system (BIO-RAD). The membranes\nwere blocked with 5% bovine serum albumin (BSA) in 50 mL of TBST for 1 h at\nroom temperature. Primary antibodies (Table 1) were diluted in TBST and\nincubated overnight at 4 °C on a shaker at 60 rpm. After incubation, the\nmembranes were washed three times with 10 mL TBST for 10 min each. Secondary\nantibodies (Table 1) were diluted in TBST and incubated for 1 h at room\ntemperature on the shaker. Protein detection was performed using the\nSuperSignal™ West Pico Plus Chemiluminescent Substrate (Thermo Fisher\nScientific). Equal volumes of enhancer solution and stable peroxide solution\nwere applied to the membrane and incubated on a shaker at 60 rpm for 5 min, after\nwhich the membrane was imaged. \n\n\n\n\n\n \n\n\n\n\n\nStatistical\nanalysis: The membrane images were analyzed\nusing ImageJ-win 64 to measure the intensity of the antibody bands. Then, the\ndata was normalized by dividing the band of interest by the band of the\nhousekeeping gene, β-Actin. Next, we averaged the normalized expression of the\nWT group (WT mean). Finally, we divided the normalized expression values for\nthe WT and AS groups by the WT mean to obtain fold changes. The fold-change\ndata were analyzed using a Student’s t-test to compare WT and AS across the\ndifferent tissues. A two-way analysis of variance (ANOVA) was used to compare\ngenotype and sex-specific differences. \n\n\n\n","reagents":"STRAIN | GENOTYPE | AVAILABLE FROM | |
Ube3am-/p+ (AS) | C57BL/6J | The Jackson Laboratory | |
Ube3am+/p+ (WT) | C57BL/6J | The Jackson Laboratory | |
ANTIBODY | DILUTION | ANIMAL AND CLONALITY | AVAILABLE FROM |
anti-Lactate dehydrogenase A | 5:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
anti-Lactate dehydrogenase B | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Bethyl Laboratories |
anti-Monocarboxylate Transporter 2 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | EMD Millipore Corp |
anti-Monocarboxylate Transporter 1 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Thermo Fisher Scientific |
anti-Beta Actin | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
Goat anti-rabbit IgG(H+L), horseradish peroxidase conjugate | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Invitrogen by Thermo Fisher Scientific |
Bird L. 2014. Angelman syndrome: review of clinical and molecular aspects. The Application of Clinical Genetics : 93.
","pubmedId":"","doi":"10.2147/TACG.S57386 "},{"reference":"Dagli AI, Mathews J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2021 Apr 22]. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1144/
","pubmedId":"","doi":""},{"reference":"Leader G, Gilligan R, Whelan S, Coyne R, Caher A, White K, et al., Mannion. 2022. Relationships between challenging behavior and gastrointestinal symptoms, sleep problems, and internalizing and externalizing symptoms in children and adolescents with Angelman syndrome. Research in Developmental Disabilities 128: 104293.
","pubmedId":"","doi":"10.1016/j.ridd.2022.104293"},{"reference":"Simchi L, Panov J, Morsy O, Feuermann Y, Kaphzan H. 2020. Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation. Journal of Clinical Medicine 9: 1573.
","pubmedId":"","doi":"10.3390/jcm9051573"},{"reference":"Gupta PK, Barak S, Feuermann Y, Goobes G, Kaphzan H. 2024. 1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. Molecular Autism 15: 10.1186/s13229-024-00608-2.
","pubmedId":"","doi":"10.1186/s13229-024-00608-2"},{"reference":"Kim Y, Dube SE, Park CB. 2025. Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis. The Korean Journal of Physiology & Pharmacology 29: 1-8.
","pubmedId":"","doi":"10.4196/kjpp.24.388"},{"reference":"Medel, V., Crossley, N., Gajardo, I., Muller, E., Barros, L.F., Shine, J.M., & Sierralta, J. (2022). Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function. Proceedings of the National Academy of Sciences of the United States of America, 119 (33). Article 2204619119. https://doi.org/10.1073%2Fpnas.2204619119
","pubmedId":"","doi":"10.1073%2Fpnas.2204619119"},{"reference":"Liu Y, Beyer A, Aebersold R. 2016. On the Dependency of Cellular Protein Levels on mRNA Abundance. Cell 165: 535-550.
","pubmedId":"","doi":"10.1016/j.cell.2016.03.014"},{"reference":"Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. 2011. Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation. Cell 144: 810-823.
","pubmedId":"","doi":"10.1016/j.cell.2011.02.018"},{"reference":"Lu WT, Sun SQ, Li Y, Xu SY, Gan SW, Xu J, et al., Huang. 2018. Curcumin Ameliorates Memory Deficits by Enhancing Lactate Content and MCT2 Expression in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease. The Anatomical Record 302: 332-338.
","pubmedId":"","doi":"10.1002/ar.23969"},{"reference":"Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., et al., Yu, T. (2022). Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy, 7 (1), 305. Article 36050306. https://doi.org/10.1038%2Fs41392-022-01151-3
","pubmedId":"","doi":"10.1038%2Fs41392-022-01151-3"},{"reference":"Wang J, Cui Y, Yu Z, Wang W, Cheng X, Ji W, et al., Yang. 2019. Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis. Cell Stem Cell 25: 754-767.e9.
","pubmedId":"","doi":"10.1016/j.stem.2019.09.009 "},{"reference":"Hoshino D, Setogawa S, Kitaoka Y, Masuda H, Tamura Y, Hatta H, Yanagihara D. 2016. Exercise-induced expression of monocarboxylate transporter 2 in the cerebellum and its contribution to motor performance. Neuroscience Letters 633: 1-6.
","pubmedId":"","doi":"10.1016/j.neulet.2016.09.012"},{"reference":"Pierre K, Pellerin L. 2005. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. Journal of Neurochemistry 94: 1-14.
","pubmedId":"","doi":"10.1111/j.1471-4159.2005.03168.x"},{"reference":"Heck DH, Zhao Y, Roy S, LeDoux MS, Reiter LT. 2008. Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors. Human Molecular Genetics 17: 2181-2189.
","pubmedId":"","doi":"10.1093/hmg/ddn117"},{"reference":"Sun J, Liu Y, Moreno S, Baudry M, Bi X. 2015. Imbalanced Mechanistic Target of Rapamycin C1 and C2 Activity in the Cerebellum of Angelman Syndrome Mice Impairs Motor Function. The Journal of Neuroscience 35: 4706-4718.
","pubmedId":"","doi":"10.1523/JNEUROSCI.4276-14.2015"}],"title":"Lactate Dehydrogenase B Expression in Cerebellum of Adult Ube3a m-/p+ Mice
","reviews":[],"curatorReviews":[]},{"id":"466a1ec5-cfdf-409e-9a5c-46a7ec8917dc","decision":"revise","abstract":"Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of the maternal allele of the UBE3A gene, which encodes a protein essential for ubiquitin-mediated protein degradation. AS mouse models exhibit elevated lactate and acetate levels and increased Ldha expression in fibroblasts. We hypothesize that maternal UBE3A loss alters the protein levels of LDHA, LDHB, MCT2, and MCT1, contributing to elevated brain lactate levels. Western blot analysis of the cerebellum from adult Ube3am-/p+ AS and wild-type mice reveals significant sex- and genotype-specific differences in LDHB expression. Loss of Ube3a alters the expression of LDHB in the cerebellum.
","acknowledgements":"","authors":[{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico"],"departments":["Biomedical Sciences "],"credit":["conceptualization","methodology","formalAnalysis","investigation","project","validation","writing_originalDraft","writing_reviewEditing"],"email":"mramosrivera5@pucpr.edu","firstName":"Miriam Arlene","lastName":"Ramos Rivera","submittingAuthor":true,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":null},{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, PR"],"departments":["Natural Sciences"],"credit":["project","resources","supervision","writing_reviewEditing"],"email":"ceidy_torres@pucpr.edu","firstName":"Ceidy","lastName":"Torres-Ortiz","submittingAuthor":false,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":null}],"awards":[],"conflictsOfInterest":"The authors declare that there are no conflicts of interest present.
","dataTable":{"url":null},"extendedData":[],"funding":"\n\n\n\nThe research was supported by funding provided to Dr. Ceidy Torres Laboratory by the Scientific Research\nCenter of the Pontifical Catholic University of Puerto Rico.\n\n\n\n","image":{"url":"https://portal.micropublication.org/uploads/3c7e570e63dcd61e2f5fd8f4ec672c47.png"},"imageCaption":"Note: Western Blots a, b, c, and d show the antibody bands of β-Actin (45 kDa), LDHA (37kDa), LDHB (36 kDa), MCT2 (52 kDa), and MCT1 (51 kDa) in the cerebellum, while m, n, and o show these in the hippocampus. Half of the samples are males (1-10), and the other half are females (11-20). The samples are intercalated, starting with WT, then AS, and so on. Graphs e, f, g, and h show protein expression of LDHA, LDHB, MCT2, and MCT1 in the cerebellum, while p, q, r, and s show these in the hippocampus. (f) Student's T-Test (N=20) found a significant difference in LDHB fold change between AS and WT (P=0.0113). Graphs i, j, k, and l compare gender and genotype using Two-Way ANOVA in the cerebellum, while t, u, v, and w show these in the hippocampus (WT = Green, AS = Purple). There are no significant differences in (i, k, l, t, u, v, and w). (j) Two-Way ANOVA reports a significant LDHB fold change difference in cerebellum AS and WT males (P=0.0128, N=10 per group).
","imageTitle":"LDHA, LDHB, MCT2, and MCT1 Protein Expression in the Cerebellum and Hippocampus
","methods":"\n\n\n\nWestern Blot\nAnalysis: \n\n\n\n\n\nThe\nhippocampus and cerebellum frozen tissues were homogenized in 300 μL RIPA\nbuffer (50 mM Tris-HCl, 150 mM NaCl, 1% NP-40, 0.5% sodium deoxycholate, 0.1%\nSDS) supplemented with protease and phosphatase inhibitors (Pierce TM Protease and Phosphatase Inhibitor Mini Tablets, Thermo Scientific). The protein concentration was determined\nusing the Qubit Protein BR Assay Kit (Invitrogen, now\nThermo Fisher Scientific) as per the manufacturer’s\ninstructions. The protein was denatured with 5x Laemmli sample buffer (10%\nsodium dodecyl sulfate, 25% 2-mercaptoethanol, 30% glycerol, 0.05% bromophenol\nblue, 292 mM Tris HCl pH 6.8) at 95°C for 10 minutes before loading onto a 4-15%\ngradient polyacrylamide gel (BIO-RAD Criterion™ TGX™ Precast Gels) and\nelectrophoresing at 80V in 1x running buffer (25 mM Tris, 192 mM glycine, 0,1%\nSDS, pH 8.3) for 1.5 hr. 10 µg was loaded to visualize the expression of LDHA,\nLDHB, MTC1 and MCT2. The proteins were\ntransferred to a 0.2 µm PVDF membrane at 25V for 7 minutes in 1x transfer\nbuffer (Trans-Blot Turbo 5x Transfer Buffer, BIO-RAD) using the Trans-Blot Turbo system (BIO-RAD). The membranes\nwere blocked with 5% bovine serum albumin (BSA) in 50 mL of TBST for 1 h at\nroom temperature. Primary antibodies (Table 1) were diluted in TBST and\nincubated overnight at 4 °C on a shaker at 60 rpm. After incubation, the\nmembranes were washed three times with 10 mL TBST for 10 min each. Secondary\nantibodies (Table 1) were diluted in TBST and incubated for 1 h at room\ntemperature on the shaker. Protein detection was performed using the\nSuperSignal™ West Pico Plus Chemiluminescent Substrate (Thermo Fisher\nScientific). Equal volumes of enhancer solution and stable peroxide solution\nwere applied to the membrane and incubated on a shaker at 60 rpm for 5 min, after\nwhich the membrane was imaged. \n\n\n\n\n\n \n\n\n\n\n\nStatistical\nanalysis: The membrane images were analyzed\nusing ImageJ-win 64 to measure the intensity of the antibody bands. Then, the\ndata was normalized by dividing the band of interest by the band of the\nhousekeeping gene, β-Actin. Next, we averaged the normalized expression of the\nWT group (WT mean). Finally, we divided the normalized expression values for\nthe WT and AS groups by the WT mean to obtain fold changes. The fold-change\ndata were analyzed using a Student’s t-test to compare WT and AS across the\ndifferent tissues. A two-way analysis of variance (ANOVA) was used to compare\ngenotype and sex-specific differences. \n\n\n\n","reagents":"STRAIN | GENOTYPE | AVAILABLE FROM | |
Ube3am-/p+ (AS) | C57BL/6J | The Jackson Laboratory | |
Ube3am+/p+ (WT) | C57BL/6J | The Jackson Laboratory | |
ANTIBODY | DILUTION | ANIMAL AND CLONALITY | AVAILABLE FROM |
anti-Lactate dehydrogenase A | 5:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
anti-Lactate dehydrogenase B | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Bethyl Laboratories |
anti-Monocarboxylate Transporter 2 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | EMD Millipore Corp |
anti-Monocarboxylate Transporter 1 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Thermo Fisher Scientific |
anti-Beta Actin | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
Goat anti-rabbit IgG(H+L), horseradish peroxidase conjugate | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Invitrogen by Thermo Fisher Scientific |
Bird L. 2014. Angelman syndrome: review of clinical and molecular aspects. The Application of Clinical Genetics : 93.
","pubmedId":"","doi":"10.2147/TACG.S57386 "},{"reference":"Dagli AI, Mathews J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2021 Apr 22]. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1144/
","pubmedId":"","doi":""},{"reference":"Leader G, Gilligan R, Whelan S, Coyne R, Caher A, White K, et al., Mannion. 2022. Relationships between challenging behavior and gastrointestinal symptoms, sleep problems, and internalizing and externalizing symptoms in children and adolescents with Angelman syndrome. Research in Developmental Disabilities 128: 104293.
","pubmedId":"","doi":"10.1016/j.ridd.2022.104293"},{"reference":"Simchi L, Panov J, Morsy O, Feuermann Y, Kaphzan H. 2020. Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation. Journal of Clinical Medicine 9: 1573.
","pubmedId":"","doi":"10.3390/jcm9051573"},{"reference":"Gupta PK, Barak S, Feuermann Y, Goobes G, Kaphzan H. 2024. 1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. Molecular Autism 15: 10.1186/s13229-024-00608-2.
","pubmedId":"","doi":"10.1186/s13229-024-00608-2"},{"reference":"Kim Y, Dube SE, Park CB. 2025. Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis. The Korean Journal of Physiology & Pharmacology 29: 1-8.
","pubmedId":"","doi":"10.4196/kjpp.24.388"},{"reference":"Medel, V., Crossley, N., Gajardo, I., Muller, E., Barros, L.F., Shine, J.M., & Sierralta, J. (2022). Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function. Proceedings of the National Academy of Sciences of the United States of America, 119 (33). Article 2204619119. https://doi.org/10.1073%2Fpnas.2204619119
","pubmedId":"","doi":"10.1073%2Fpnas.2204619119"},{"reference":"Liu Y, Beyer A, Aebersold R. 2016. On the Dependency of Cellular Protein Levels on mRNA Abundance. Cell 165: 535-550.
","pubmedId":"","doi":"10.1016/j.cell.2016.03.014"},{"reference":"Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. 2011. Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation. Cell 144: 810-823.
","pubmedId":"","doi":"10.1016/j.cell.2011.02.018"},{"reference":"Lu WT, Sun SQ, Li Y, Xu SY, Gan SW, Xu J, et al., Huang. 2018. Curcumin Ameliorates Memory Deficits by Enhancing Lactate Content and MCT2 Expression in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease. The Anatomical Record 302: 332-338.
","pubmedId":"","doi":"10.1002/ar.23969"},{"reference":"Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., et al., Yu, T. (2022). Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy, 7 (1), 305. Article 36050306. https://doi.org/10.1038%2Fs41392-022-01151-3
","pubmedId":"","doi":"10.1038%2Fs41392-022-01151-3"},{"reference":"Wang J, Cui Y, Yu Z, Wang W, Cheng X, Ji W, et al., Yang. 2019. Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis. Cell Stem Cell 25: 754-767.e9.
","pubmedId":"","doi":"10.1016/j.stem.2019.09.009 "},{"reference":"Hoshino D, Setogawa S, Kitaoka Y, Masuda H, Tamura Y, Hatta H, Yanagihara D. 2016. Exercise-induced expression of monocarboxylate transporter 2 in the cerebellum and its contribution to motor performance. Neuroscience Letters 633: 1-6.
","pubmedId":"","doi":"10.1016/j.neulet.2016.09.012"},{"reference":"Pierre K, Pellerin L. 2005. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. Journal of Neurochemistry 94: 1-14.
","pubmedId":"","doi":"10.1111/j.1471-4159.2005.03168.x"},{"reference":"Heck DH, Zhao Y, Roy S, LeDoux MS, Reiter LT. 2008. Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors. Human Molecular Genetics 17: 2181-2189.
","pubmedId":"","doi":"10.1093/hmg/ddn117"},{"reference":"Sun J, Liu Y, Moreno S, Baudry M, Bi X. 2015. Imbalanced Mechanistic Target of Rapamycin C1 and C2 Activity in the Cerebellum of Angelman Syndrome Mice Impairs Motor Function. The Journal of Neuroscience 35: 4706-4718.
","pubmedId":"","doi":"10.1523/JNEUROSCI.4276-14.2015"}],"title":"Lactate Dehydrogenase B Expression in Cerebellum of Adult Ube3a m-/p+ Mice
","reviews":[],"curatorReviews":[]},{"id":"4dc683d7-e679-4936-9c61-a25733acfca1","decision":"edit","abstract":"Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of the maternal allele of the UBE3A gene, which encodes a protein essential for ubiquitin-mediated protein degradation. AS mouse models exhibit elevated lactate and acetate levels and increased Ldha expression in fibroblasts. We hypothesize that maternal UBE3A loss alters the protein levels of LDHA, LDHB, MCT2, and MCT1, contributing to elevated brain lactate levels. Western blot analysis of the cerebellum from adult Ube3am-/p+ AS and wild-type mice reveals significant sex- and genotype-specific differences in LDHB expression. Loss of Ube3a alters the expression of LDHB in the cerebellum.
","acknowledgements":"","authors":[{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico"],"departments":["Biomedical Sciences "],"credit":["conceptualization","methodology","formalAnalysis","investigation","project","validation","writing_originalDraft","writing_reviewEditing"],"email":"mramosrivera5@pucpr.edu","firstName":"Miriam Arlene","lastName":"Ramos Rivera","submittingAuthor":true,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":null},{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, PR"],"departments":["Natural Sciences"],"credit":["project","resources","supervision","writing_reviewEditing"],"email":"ceidy_torres@pucpr.edu","firstName":"Ceidy","lastName":"Torres-Ortiz","submittingAuthor":false,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":null}],"awards":[],"conflictsOfInterest":"The authors declare that there are no conflicts of interest present.
","dataTable":{"url":null},"extendedData":[],"funding":"\n\n\n\nThe research was supported by funding provided to Dr. Ceidy Torres Laboratory by the Scientific Research\nCenter of the Pontifical Catholic University of Puerto Rico.\n\n\n\n","image":{"url":"https://portal.micropublication.org/uploads/d2d74ef054e528633b7c8604841c5ca6.png"},"imageCaption":"Note: Western Blots a, b, c, and d show antibody bands for β-Actin (45 kDa), LDHA (37 kDa), LDHB (36 kDa), MCT2 (52 kDa), and MCT1 (51 kDa) in the cerebellum, while m, n, and o show these in the hippocampus. Half of the samples are males (1-10), and the other half are females (11-20). Samples are intercalated, starting with WT, then AS, and so on. Graphs e, f, g, and h show protein expression of LDHA, LDHB, MCT2, and MCT1 in the cerebellum, while p, q, r, and s show these in the hippocampus. Graphs p and t correspond to MCT2, and graphs q and u correspond to LDHA in the hippocampus. (f) Student's t-test (N=20) found a significant difference in LDHB fold change between AS and WT (P=0.0113). Graphs i, j, k, and l compare gender and genotype using Two-way ANOVA in the cerebellum, while t, u, v, and w show these in the hippocampus (WT = Green, AS = Purple). There are no significant differences in (I, k, l, t, u, v, and w). (j) Two-way ANOVA reports a significant LDHB difference in cerebellum males (P=0.0128, N=10 per group).
","imageTitle":"LDHA, LDHB, MCT2, and MCT1 Protein Expression in the Cerebellum and Hippocampus
","methods":"\n\n\n\nWestern Blot\nAnalysis: \n\n\n\n\n\nThe\nhippocampus and cerebellum frozen tissues were homogenized in 300 μL RIPA\nbuffer (50 mM Tris-HCl, 150 mM NaCl, 1% NP-40, 0.5% sodium deoxycholate, 0.1%\nSDS) supplemented with protease and phosphatase inhibitors (Pierce TM Protease and Phosphatase Inhibitor Mini Tablets, Thermo Scientific). The protein concentration was determined\nusing the Qubit Protein BR Assay Kit (Invitrogen, now\nThermo Fisher Scientific) as per the manufacturer’s\ninstructions. The protein was denatured with 5x Laemmli sample buffer (10%\nsodium dodecyl sulfate, 25% 2-mercaptoethanol, 30% glycerol, 0.05% bromophenol\nblue, 292 mM Tris HCl pH 6.8) at 95°C for 10 minutes before loading onto a 4-15%\ngradient polyacrylamide gel (BIO-RAD Criterion™ TGX™ Precast Gels) and\nelectrophoresing at 80V in 1x running buffer (25 mM Tris, 192 mM glycine, 0,1%\nSDS, pH 8.3) for 1.5 hr. 10 µg was loaded to visualize the expression of LDHA,\nLDHB, MTC1 and MCT2. The proteins were\ntransferred to a 0.2 µm PVDF membrane at 25V for 7 minutes in 1x transfer\nbuffer (Trans-Blot Turbo 5x Transfer Buffer, BIO-RAD) using the Trans-Blot Turbo system (BIO-RAD). The membranes\nwere blocked with 5% bovine serum albumin (BSA) in 50 mL of TBST for 1 h at\nroom temperature. Primary antibodies (Table 1) were diluted in TBST and\nincubated overnight at 4 °C on a shaker at 60 rpm. After incubation, the\nmembranes were washed three times with 10 mL TBST for 10 min each. Secondary\nantibodies (Table 1) were diluted in TBST and incubated for 1 h at room\ntemperature on the shaker. Protein detection was performed using the\nSuperSignal™ West Pico Plus Chemiluminescent Substrate (Thermo Fisher\nScientific). Equal volumes of enhancer solution and stable peroxide solution\nwere applied to the membrane and incubated on a shaker at 60 rpm for 5 min, after\nwhich the membrane was imaged. \n\n\n\n\n\n \n\n\n\n\n\nStatistical\nanalysis: The membrane images were analyzed\nusing ImageJ-win 64 to measure the intensity of the antibody bands. Then, the\ndata was normalized by dividing the band of interest by the band of the\nhousekeeping gene, β-Actin. Next, we averaged the normalized expression of the\nWT group (WT mean). Finally, we divided the normalized expression values for\nthe WT and AS groups by the WT mean to obtain fold changes. The fold-change\ndata were analyzed using a Student’s t-test to compare WT and AS across the\ndifferent tissues. A two-way analysis of variance (ANOVA) was used to compare\ngenotype and sex-specific differences. \n\n\n\n","reagents":"STRAIN | GENOTYPE | AVAILABLE FROM | |
Ube3am-/p+ (AS) | C57BL/6J | The Jackson Laboratory | |
Ube3am+/p+ (WT) | C57BL/6J | The Jackson Laboratory | |
ANTIBODY | DILUTION | ANIMAL AND CLONALITY | AVAILABLE FROM |
anti-Lactate dehydrogenase A | 5:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
anti-Lactate dehydrogenase B | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Bethyl Laboratories |
anti-Monocarboxylate Transporter 2 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | EMD Millipore Corp |
anti-Monocarboxylate Transporter 1 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Thermo Fisher Scientific |
anti-Beta Actin | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
Goat anti-rabbit IgG(H+L), horseradish peroxidase conjugate | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Invitrogen by Thermo Fisher Scientific |
Bird L. 2014. Angelman syndrome: review of clinical and molecular aspects. The Application of Clinical Genetics : 93.
","pubmedId":"","doi":"10.2147/TACG.S57386 "},{"reference":"Dagli AI, Mathews J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2021 Apr 22]. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1144/
","pubmedId":"","doi":""},{"reference":"Leader G, Gilligan R, Whelan S, Coyne R, Caher A, White K, et al., Mannion. 2022. Relationships between challenging behavior and gastrointestinal symptoms, sleep problems, and internalizing and externalizing symptoms in children and adolescents with Angelman syndrome. Research in Developmental Disabilities 128: 104293.
","pubmedId":"","doi":"10.1016/j.ridd.2022.104293"},{"reference":"Simchi L, Panov J, Morsy O, Feuermann Y, Kaphzan H. 2020. Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation. Journal of Clinical Medicine 9: 1573.
","pubmedId":"","doi":"10.3390/jcm9051573"},{"reference":"Gupta PK, Barak S, Feuermann Y, Goobes G, Kaphzan H. 2024. 1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. Molecular Autism 15: 10.1186/s13229-024-00608-2.
","pubmedId":"","doi":"10.1186/s13229-024-00608-2"},{"reference":"Kim Y, Dube SE, Park CB. 2025. Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis. The Korean Journal of Physiology & Pharmacology 29: 1-8.
","pubmedId":"","doi":"10.4196/kjpp.24.388"},{"reference":"Medel, V., Crossley, N., Gajardo, I., Muller, E., Barros, L.F., Shine, J.M., & Sierralta, J. (2022). Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function. Proceedings of the National Academy of Sciences of the United States of America, 119 (33). Article 2204619119. https://doi.org/10.1073%2Fpnas.2204619119
","pubmedId":"","doi":"10.1073%2Fpnas.2204619119"},{"reference":"Liu Y, Beyer A, Aebersold R. 2016. On the Dependency of Cellular Protein Levels on mRNA Abundance. Cell 165: 535-550.
","pubmedId":"","doi":"10.1016/j.cell.2016.03.014"},{"reference":"Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. 2011. Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation. Cell 144: 810-823.
","pubmedId":"","doi":"10.1016/j.cell.2011.02.018"},{"reference":"Lu WT, Sun SQ, Li Y, Xu SY, Gan SW, Xu J, et al., Huang. 2018. Curcumin Ameliorates Memory Deficits by Enhancing Lactate Content and MCT2 Expression in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease. The Anatomical Record 302: 332-338.
","pubmedId":"","doi":"10.1002/ar.23969"},{"reference":"Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., et al., Yu, T. (2022). Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy, 7 (1), 305. Article 36050306. https://doi.org/10.1038%2Fs41392-022-01151-3
","pubmedId":"","doi":"10.1038%2Fs41392-022-01151-3"},{"reference":"Wang J, Cui Y, Yu Z, Wang W, Cheng X, Ji W, et al., Yang. 2019. Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis. Cell Stem Cell 25: 754-767.e9.
","pubmedId":"","doi":"10.1016/j.stem.2019.09.009 "},{"reference":"Hoshino D, Setogawa S, Kitaoka Y, Masuda H, Tamura Y, Hatta H, Yanagihara D. 2016. Exercise-induced expression of monocarboxylate transporter 2 in the cerebellum and its contribution to motor performance. Neuroscience Letters 633: 1-6.
","pubmedId":"","doi":"10.1016/j.neulet.2016.09.012"},{"reference":"Pierre K, Pellerin L. 2005. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. Journal of Neurochemistry 94: 1-14.
","pubmedId":"","doi":"10.1111/j.1471-4159.2005.03168.x"},{"reference":"Heck DH, Zhao Y, Roy S, LeDoux MS, Reiter LT. 2008. Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors. Human Molecular Genetics 17: 2181-2189.
","pubmedId":"","doi":"10.1093/hmg/ddn117"},{"reference":"Sun J, Liu Y, Moreno S, Baudry M, Bi X. 2015. Imbalanced Mechanistic Target of Rapamycin C1 and C2 Activity in the Cerebellum of Angelman Syndrome Mice Impairs Motor Function. The Journal of Neuroscience 35: 4706-4718.
","pubmedId":"","doi":"10.1523/JNEUROSCI.4276-14.2015"}],"title":"Lactate Dehydrogenase B Expression in Cerebellum of Adult Ube3a m-/p+ Mice
","reviews":[],"curatorReviews":[]},{"id":"73289dda-31d6-4a5d-896a-be7b711f48fe","decision":"accept","abstract":"Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of the maternal allele of the UBE3A gene, which encodes a protein essential for ubiquitin-mediated protein degradation. AS mouse models exhibit elevated lactate and acetate levels and increased Ldha expression in fibroblasts. We hypothesize that maternal UBE3A loss alters the protein levels of LDHA, LDHB, MCT2, and MCT1, contributing to elevated brain lactate levels. Western blot analysis of the cerebellum from adult Ube3am-/p+ AS and wild-type mice reveals significant sex- and genotype-specific differences in LDHB expression. Loss of Ube3a alters the expression of LDHB in the cerebellum.
","acknowledgements":"","authors":[{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico"],"departments":["Biomedical Sciences "],"credit":["conceptualization","methodology","formalAnalysis","investigation","project","validation","writing_originalDraft","writing_reviewEditing"],"email":"mramosrivera5@pucpr.edu","firstName":"Miriam Arlene","lastName":"Ramos Rivera","submittingAuthor":true,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":null},{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, PR"],"departments":["Natural Sciences"],"credit":["project","resources","supervision","writing_reviewEditing"],"email":"ceidy_torres@pucpr.edu","firstName":"Ceidy","lastName":"Torres-Ortiz","submittingAuthor":false,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":null}],"awards":[],"conflictsOfInterest":"The authors declare that there are no conflicts of interest present.
","dataTable":{"url":null},"extendedData":[],"funding":"\n\n\n\nThe research was supported by funding provided to Dr. Ceidy Torres Laboratory by the Scientific Research\nCenter of the Pontifical Catholic University of Puerto Rico.\n\n\n\n","image":{"url":"https://portal.micropublication.org/uploads/d2d74ef054e528633b7c8604841c5ca6.png"},"imageCaption":"Note: Western Blots a, b, c, and d show antibody bands for β-Actin (45 kDa), LDHA (37 kDa), LDHB (36 kDa), MCT2 (52 kDa), and MCT1 (51 kDa) in the cerebellum, while m, n, and o show these in the hippocampus. Half of the samples are males (1-10), and the other half are females (11-20). Samples are intercalated, starting with WT, then AS, and so on. Graphs e, f, g, and h show protein expression of LDHA, LDHB, MCT2, and MCT1 in the cerebellum, while p, q, r, and s show these in the hippocampus. Graphs p and t correspond to MCT2, and graphs q and u correspond to LDHA in the hippocampus. (f) Student's t-test (N=20) found a significant difference in LDHB fold change between AS and WT (P=0.0113). Graphs i, j, k, and l compare gender and genotype using Two-way ANOVA in the cerebellum, while t, u, v, and w show these in the hippocampus (WT = Green, AS = Purple). There are no significant differences in (I, k, l, t, u, v, and w). (j) Two-way ANOVA reports a significant LDHB difference in cerebellum males (P=0.0128, N=10 per group).
","imageTitle":"LDHA, LDHB, MCT2, and MCT1 Protein Expression in the Cerebellum and Hippocampus
","methods":"Western Blot Analysis: The hippocampus and cerebellum frozen tissues were homogenized in 300 μL RIPA buffer (50 mM Tris-HCl, 150 mM NaCl, 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS) supplemented with protease and phosphatase inhibitors (Pierce TM Protease and Phosphatase Inhibitor Mini Tablets, Thermo Scientific). The protein concentration was determined using the Qubit Protein BR Assay Kit (Invitrogen, now Thermo Fisher Scientific) as per the manufacturer’s instructions. The protein was denatured with 5x Laemmli sample buffer (10% sodium dodecyl sulfate, 25% 2-mercaptoethanol, 30% glycerol, 0.05% bromophenol blue, 292 mM Tris HCl pH 6.8) at 95°C for 10 minutes before loading onto a 4-15% gradient polyacrylamide gel (BIO-RAD Criterion™ TGX™ Precast Gels) and electrophoresing at 80V in 1x running buffer (25 mM Tris, 192 mM glycine, 0,1% SDS, pH 8.3) for 1.5 hr. 10 µg was loaded to visualize the expression of LDHA, LDHB, MTC1 and MCT2. The proteins were transferred to a 0.2 µm PVDF membrane at 25V for 7 minutes in 1x transfer buffer (Trans-Blot Turbo 5x Transfer Buffer, BIO-RAD) using the Trans-Blot Turbo system (BIO-RAD). The membranes were blocked with 5% bovine serum albumin (BSA) in 50 mL of TBST for 1 h at room temperature. Primary antibodies (Table 1) were diluted in TBST and incubated overnight at 4 °C on a shaker at 60 rpm. After incubation, the membranes were washed three times with 10 mL TBST for 10 min each. Secondary antibodies (Table 1) were diluted in TBST and incubated for 1 h at room temperature on the shaker. Protein detection was performed using the SuperSignal™ West Pico Plus Chemiluminescent Substrate (Thermo Fisher Scientific). Equal volumes of enhancer solution and stable peroxide solution were applied to the membrane and incubated on a shaker at 60 rpm for 5 min, after which the membrane was imaged. Statistical analysis: The membrane images were analyzed using ImageJ-win 64 to measure the intensity of the antibody bands. Then, the data was normalized by dividing the band of interest by the band of the housekeeping gene, β-Actin. Next, we averaged the normalized expression of the WT group (WT mean). Finally, we divided the normalized expression values for the WT and AS groups by the WT mean to obtain fold changes. The fold-change data were analyzed using a Student’s t-test to compare WT and AS across the different tissues. A two-way analysis of variance (ANOVA) was used to compare genotype and sex-specific differences.
","reagents":"STRAIN | GENOTYPE | AVAILABLE FROM | |
Ube3am-/p+ (AS) | C57BL/6J | The Jackson Laboratory | |
Ube3am+/p+ (WT) | C57BL/6J | The Jackson Laboratory | |
ANTIBODY | DILUTION | ANIMAL AND CLONALITY | AVAILABLE FROM |
anti-Lactate dehydrogenase A | 5:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
anti-Lactate dehydrogenase B | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Bethyl Laboratories |
anti-Monocarboxylate Transporter 2 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | EMD Millipore Corp |
anti-Monocarboxylate Transporter 1 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Thermo Fisher Scientific |
anti-Beta Actin | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
Goat anti-rabbit IgG(H+L), horseradish peroxidase conjugate | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Invitrogen by Thermo Fisher Scientific |
Ubiquitin Protein Ligase E3A (UBE3A) is vital for nervous system development, neuron maturation, synaptic plasticity, and brain growth (Leader et al., 2022; Bird, 2014). Only in neurons does this gene undergo maternal imprinting defects or deletions; consequently, loss of the maternal allele results in Angelman Syndrome (AS), a well-characterized neurodevelopmental disorder (Dagli et al., 1998; Sun et al., 2019). Recent studies report alterations in lactate metabolism in AS, including increased Lactate dehydrogenase A (Ldha) gene expression in embryonic fibroblasts of the AS model (Simchi et al., 2020) and elevated lactate levels in lyophilized AS brain samples (Gupta et al., 2024). According to the astrocyte–neuron lactate shuttle hypothesis, astrocytes produce lactate from glucose via LDHA, which is transported into neurons through Monocarboxylate Transporter (MCT2) and converted back to pyruvate by LDHB to support neuronal energy metabolism (Liu et al., 2017; Medel et al., 2022; Kim et al., 2025). Lactate plays a role in learning and memory processes (Suzuki et al., 2012). Also, it serves as a signaling molecule in various mechanisms, including the regulation of energy metabolism, immunological responses, memory formation, and muscle contraction (Li et al., 2022). In Alzheimer’s disease models, lower hippocampal lactate levels correlate with memory impairment (Lu et al., 2019), and altered expression of lactate transporters (MCT1, MCT2, MCT4) indicates impaired lactate signaling in neurological disorders (Wang et al., 2019). In the cerebellum, which regulates motor coordination, posture, and balance, disruptions in the lactate shuttle impair motor performance, as shown by reduced function upon MCT2 inhibition in mice (Hoshino et al., 2016; Pierre and Pellerin, 2005; Li et al., 2022). Studying lactate pathways in AS helps to understand how elevated lactate affects the adult brain. This study examines LDHA, LDHB, MCT2, and MCT1 levels in the hippocampus and cerebellum of Ube3a m-/p+ (AS) compared with wild-type (WT) mice. We hypothesize that maternal UBE3A loss affects the expression of LDHA, LDHB, MCT2, and MCT1, possibly contributing to elevated lactate levels in AS. The protein expression fold changes of LDHA, LDHB, MCT2, and MCT1 were assessed by Western blot in hippocampal and cerebellar tissues from adult male and female AS and WT mice. The data were analyzed using a Student’s t-test to compare genotypes and a two-way ANOVA to assess sex differences across genotypes. In the hippocampus, no significant differences were observed in LDHA, LDHB, MCT2, or MCT1 expression between AS and WT mice (Fig. k-n). Also, any sex-specific differences in protein expression between AS and WT mice (Fig. o-r). Conversely, LDHB expression in the cerebellum was significantly lower in AS mice (p = 0.0113, Fig. b-c) while LDHA, MCT1, and MCT2 showed no significant differences (Fig. a, d, e). The reduced LDHB expression in the cerebellum of AS mice is attributable to the male group (p=0.0128, Fig. g-h). These results suggest that reduced LDHB may impair lactate-to-pyruvate conversion, decreasing pyruvate availability, elevating lactate levels, and disrupting the TCA cycle, ultimately leading to bioenergetic deficits and motor impairments in the cerebellum, particularly in adult males. These results confirm previous reports that AS mice exhibit motor deficiencies in motor tasks, such as decreased grip strength and performance on the raised beam task (Heck et al., 2008), and higher latency to fall on the rotarod test (Sun et al., 2015). The loss of maternal UBE3A in the adult Ube3a m-/p+ AS mouse model affects LDHB protein expression in the cerebellum but not in the hippocampus. This suggests that the absence of maternal UBE3A may specifically influence the expression of specific metabolic proteins in the cerebellum. Observations suggest lactate may increase during early development in AS mice (Gupta et al., 2024), possibly affecting LDHs and MCTs in adulthood. These studies contribute to our understanding of lactate metabolism in AS and may inform therapeutic approaches, highlighting the need for continued research given the limited number of reports in this field.
","references":[{"reference":"Bird L. 2014. Angelman syndrome: review of clinical and molecular aspects. The Application of Clinical Genetics : 93.
","pubmedId":"","doi":"10.2147/TACG.S57386 "},{"reference":"Dagli AI, Mathews J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2021 Apr 22]. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1144/
","pubmedId":"","doi":""},{"reference":"Gupta PK, Barak S, Feuermann Y, Goobes G, Kaphzan H. 2024. 1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. Molecular Autism 15: 10.1186/s13229-024-00608-2.
","pubmedId":"","doi":"10.1186/s13229-024-00608-2"},{"reference":"Heck DH, Zhao Y, Roy S, LeDoux MS, Reiter LT. 2008. Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors. Human Molecular Genetics 17: 2181-2189.
","pubmedId":"","doi":"10.1093/hmg/ddn117"},{"reference":"Hoshino D, Setogawa S, Kitaoka Y, Masuda H, Tamura Y, Hatta H, Yanagihara D. 2016. Exercise-induced expression of monocarboxylate transporter 2 in the cerebellum and its contribution to motor performance. Neuroscience Letters 633: 1-6.
","pubmedId":"","doi":"10.1016/j.neulet.2016.09.012"},{"reference":"Kim Y, Dube SE, Park CB. 2025. Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis. The Korean Journal of Physiology & Pharmacology 29: 1-8.
","pubmedId":"","doi":"10.4196/kjpp.24.388"},{"reference":"Leader G, Gilligan R, Whelan S, Coyne R, Caher A, White K, et al., Mannion. 2022. Relationships between challenging behavior and gastrointestinal symptoms, sleep problems, and internalizing and externalizing symptoms in children and adolescents with Angelman syndrome. Research in Developmental Disabilities 128: 104293.
","pubmedId":"","doi":"10.1016/j.ridd.2022.104293"},{"reference":"Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., et al., Yu, T. (2022). Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy, 7 (1), 305. Article 36050306. https://doi.org/10.1038%2Fs41392-022-01151-3
","pubmedId":"","doi":"10.1038%2Fs41392-022-01151-3"},{"reference":"Liu Y, Beyer A, Aebersold R. 2016. On the Dependency of Cellular Protein Levels on mRNA Abundance. Cell 165: 535-550.
","pubmedId":"","doi":"10.1016/j.cell.2016.03.014"},{"reference":"Lu WT, Sun SQ, Li Y, Xu SY, Gan SW, Xu J, et al., Huang. 2018. Curcumin Ameliorates Memory Deficits by Enhancing Lactate Content and MCT2 Expression in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease. The Anatomical Record 302: 332-338.
","pubmedId":"","doi":"10.1002/ar.23969"},{"reference":"Medel, V., Crossley, N., Gajardo, I., Muller, E., Barros, L.F., Shine, J.M., & Sierralta, J. (2022). Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function. Proceedings of the National Academy of Sciences of the United States of America, 119 (33). Article 2204619119. https://doi.org/10.1073%2Fpnas.2204619119
","pubmedId":"","doi":"10.1073%2Fpnas.2204619119"},{"reference":"Pierre K, Pellerin L. 2005. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. Journal of Neurochemistry 94: 1-14.
","pubmedId":"","doi":"10.1111/j.1471-4159.2005.03168.x"},{"reference":"Simchi L, Panov J, Morsy O, Feuermann Y, Kaphzan H. 2020. Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation. Journal of Clinical Medicine 9: 1573.
","pubmedId":"","doi":"10.3390/jcm9051573"},{"reference":"Sun J, Liu Y, Moreno S, Baudry M, Bi X. 2015. Imbalanced Mechanistic Target of Rapamycin C1 and C2 Activity in the Cerebellum of Angelman Syndrome Mice Impairs Motor Function. The Journal of Neuroscience 35: 4706-4718.
","pubmedId":"","doi":"10.1523/JNEUROSCI.4276-14.2015"},{"reference":"Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. 2011. Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation. Cell 144: 810-823.
","pubmedId":"","doi":"10.1016/j.cell.2011.02.018"},{"reference":"Wang J, Cui Y, Yu Z, Wang W, Cheng X, Ji W, et al., Yang. 2019. Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis. Cell Stem Cell 25: 754-767.e9.
","pubmedId":"","doi":"10.1016/j.stem.2019.09.009 "}],"title":"Lactate Dehydrogenase B Expression in Cerebellum of Adult Ube3a m-/p+ Mice
","reviews":[],"curatorReviews":[]},{"id":"678c5af8-149a-4bca-bc57-a8083504f05b","decision":"publish","abstract":"Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of the maternal allele of the UBE3A gene, which encodes a protein essential for ubiquitin-mediated protein degradation. AS mouse models exhibit elevated lactate and acetate levels and increased Ldha gene expression in fibroblasts. We hypothesize that maternal Ube3a loss alters the protein levels of Ldha, Ldhb, Mct2, and Mct1, contributing to elevated brain lactate levels. Western blot analysis of the cerebellum from adult Ube3am-/p+ AS and wild-type mice reveals significant sex- and genotype-specific differences in Ldhb expression. Loss of Ube3a alters the expression of Ldhb in the cerebellum.
","acknowledgements":"","authors":[{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico"],"departments":["Department of Biomedical Sciences "],"credit":["conceptualization","methodology","formalAnalysis","investigation","project","validation","writing_originalDraft","writing_reviewEditing"],"email":"mramosrivera5@pucpr.edu","firstName":"Miriam Arlene","lastName":"Ramos Rivera","submittingAuthor":true,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":null},{"affiliations":["Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico"],"departments":["Department of Natural Sciences"],"credit":["project","resources","supervision","writing_reviewEditing"],"email":"ceidy_torres@pucpr.edu","firstName":"Ceidy","lastName":"Torres-Ortiz","submittingAuthor":false,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":null}],"awards":[],"conflictsOfInterest":"The authors declare that there are no conflicts of interest present.
","dataTable":{"url":null},"extendedData":[],"funding":"\n\n\n\nThe research was supported by funding provided to Dr. Ceidy Torres Laboratory by the Scientific Research\nCenter of the Pontifical Catholic University of Puerto Rico.\n\n\n\n","image":{"url":"https://portal.micropublication.org/uploads/d2d74ef054e528633b7c8604841c5ca6.png"},"imageCaption":"Note: Western Blots a, b, c, and d show antibody bands for β-Actin (45 kDa), Ldha (37 kDa), Ldhb (36 kDa), Mct2 (52 kDa), and Mct1 (51 kDa) in the cerebellum, while m, n, and o show these in the hippocampus. In the gel, the samples are intercalated, starting with WT, then AS; males (1-10 wells position), and females (11-20 wells position). All mice are adults between 10 to 12 week old. Graphs e, f, g, and h show protein expression of Ldha, Ldhb, Mct2, and Mct1 in the cerebellum, while p, q, r, and s show these in the hippocampus. Graphs p and t correspond to Mct2, and graphs q and u correspond to Ldha in the hippocampus. (f) Student's t-test (N=20) found a significant difference in Ldhb fold change between AS and WT (p=0.0113). Graphs i, j, k, and l compare gender and genotype using Two-way ANOVA in the cerebellum, while t, u, v, and w show these in the hippocampus (WT = Green, AS = Purple). There are no significant differences in (i, k, l, t, u, v, and w). (j) Two-way ANOVA reports a significant Ldhb difference in cerebellum males (p=0.0128, n=10 per group).
","imageTitle":"Ldha, Ldhb, Mct2, and Mct1 Protein Expression in the Cerebellum and Hippocampus
","methods":"Western Blot Analysis:
The hippocampus and cerebellum frozen tissues were homogenized in 300 μL RIPA buffer (50 mM Tris-HCl, 150 mM NaCl, 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS) supplemented with protease and phosphatase inhibitors (Pierce TM Protease and Phosphatase Inhibitor Mini Tablets, Thermo Scientific). The protein concentration was determined using the Qubit Protein BR Assay Kit (Invitrogen, now Thermo Fisher Scientific) as per the manufacturer’s instructions. The protein was denatured with 5X Laemmli sample buffer (10% sodium dodecyl sulfate, 25% 2-mercaptoethanol, 30% glycerol, 0.05% bromophenol blue, 292 mM Tris HCl pH 6.8) at 95°C for 10 minutes before loading onto a 4-15% gradient polyacrylamide gel (BIO-RAD Criterion™ TGX™ Precast Gels) and electrophoresing at 80V in 1X running buffer (25 mM Tris, 192 mM glycine, 0,1% SDS, pH 8.3) for 1.5 hours. 10 µg was loaded to visualize the expression of Ldha, Ldhb, Mct1 and Mct2. The proteins were transferred to a 0.2 µm PVDF membrane at 25V for 7 minutes in 1X transfer buffer (Trans-Blot Turbo 5x Transfer Buffer, BIO-RAD) using the Trans-Blot Turbo system (BIO-RAD). The membranes were blocked with 5% bovine serum albumin (BSA) in 50 mL of TBST for 1 hour at room temperature. Primary antibodies (Table 1) were diluted in TBST and incubated overnight at 4 °C on a shaker at 60 rpm. After incubation, the membranes were washed three times with 10 mL TBST for 10 minutes each. Secondary antibodies (Table 1) were diluted in TBST and incubated for 1 hour at room temperature on the shaker. Protein detection was performed using the SuperSignal™ West Pico Plus Chemiluminescent Substrate (Thermo Fisher Scientific). Equal volumes of enhancer solution and stable peroxide solution were applied to the membrane and incubated on a shaker at 60 rpm for 5 minutes, after which the membrane was imaged.
Statistical analysis:
The membrane images were analyzed using ImageJ-win 64 to measure the intensity of the antibody bands. Then, the data was normalized by dividing the band of interest by the band of the housekeeping gene, β-Actin. Next, we averaged the normalized expression of the WT group (WT mean). Finally, we divided the normalized expression values for the WT and AS groups by the WT mean to obtain fold changes. The fold-change data were analyzed using a Student’s t-test to compare WT and AS across the different tissues. A two-way analysis of variance (ANOVA) was used to compare genotype and sex-specific differences.
","reagents":"Table 1: Strain Description and Antibodies Information | |||
STRAIN | GENOTYPE | AVAILABLE FROM | |
Ube3am-/p+ | C57BL/6J | The Jackson Laboratory | |
Ube3am+/p+ | C57BL/6J | The Jackson Laboratory | |
ANTIBODY | DILUTION | ANIMAL AND CLONALITY | DESCRIPTION |
anti-Lactate dehydrogenase A | 5:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
anti-Lactate dehydrogenase B | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Bethyl Laboratories |
anti-Monocarboxylate Transporter 2 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | EMD Millipore Corp |
anti-Monocarboxylate Transporter 1 | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Thermo Fisher Scientific |
anti-Beta Actin | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Cell Signaling Technology |
Goat anti-rabbit IgG(H+L), horseradish peroxidase conjugate | 1:10,000 in TBS-0.1% Tween 20 | Rabbit polyclonal | Invitrogen by Thermo Fisher Scientific |
Ubiquitin Protein Ligase E3A (UBE3A) is vital for nervous system development, neuron maturation, synaptic plasticity, and brain growth (Leader et al., 2022; Bird, 2014). Only in neurons does this gene undergo maternal imprinting defects or deletions; consequently, loss of the maternal allele results in Angelman Syndrome (AS), a well-characterized neurodevelopmental disorder (Dagli et al., 1998; Sun et al., 2019). Recent studies report alterations in lactate metabolism in AS, including increased Lactate dehydrogenase A (Ldha) gene expression in embryonic fibroblasts of the AS model (Simchi et al., 2020) and elevated lactate levels in lyophilized AS brain samples (Gupta et al., 2024). According to the astrocyte–neuron lactate shuttle hypothesis, astrocytes produce lactate from glucose via LDHA, which is transported into neurons through Monocarboxylate Transporter (MCT2) and converted back to pyruvate by LDHB to support neuronal energy metabolism (Suzuki et al., 2011; Liu et al., 2017; Medel et al., 2022; Kim et al., 2025). Also, it serves as a signaling molecule in various mechanisms, including the regulation of energy metabolism, immunological responses, memory formation, and muscle contraction (Li et al., 2022).
In Alzheimer’s disease models, lower hippocampal lactate levels correlate with memory impairment (Lu et al., 2018), and altered expression of lactate transporters (MCT1, MCT2, MCT4) indicates impaired lactate signaling in neurological disorders (Wang et al., 2019). In the cerebellum, which regulates motor coordination, posture, and balance, disruptions in the lactate shuttle impair motor performance, as shown by reduced function upon Mct2 inhibition in mice (Hoshino et al., 2016; Pierre and Pellerin, 2005; Li et al., 2022). Studying lactate pathways in AS helps to understand how elevated lactate affects the adult brain. This study examines Ldha, Ldhb, Mct2, and Mct1 levels in the hippocampus and cerebellum of Ube3a m-/p+ (AS) compared with wild-type (WT) mice. We hypothesize that maternal Ube3a loss affects the expression of Ldha, Ldhb, Mct2, and Mct1, possibly contributing to elevated lactate levels in AS. The protein expression fold changes of Ldha, Ldhb, Mct2, and Mct1 were assessed by Western blot in hippocampal and cerebellar tissues from adult male and female AS and WT mice. The data were analyzed using a Student’s t-test to compare genotypes and a two-way ANOVA to assess sex differences across genotypes.
In the hippocampus, no significant differences were observed in Ldha, Ldhb, Mct2, or Mct1 expression between AS and WT mice (Fig.1 p-s). Also, any sex-specific differences in protein expression between AS and WT mice (Fig.1 t-w). Conversely, Ldhb expression in the cerebellum was significantly lower in AS mice (p = 0.0113, Fig.1 f) while Ldha, Mct1, and Mct2 showed no significant differences (Fig. e, g, h). The reduced Ldhb expression in the cerebellum of AS mice is attributable to the male group (p=0.0128, Fig. j). These results suggest that reduced Ldhb may impair lactate-to-pyruvate conversion, decreasing pyruvate availability, elevating lactate levels, and disrupting the TCA cycle, ultimately leading to bioenergetic deficits and motor impairments in the cerebellum, particularly in adult males. These results confirm previous reports that AS mice exhibit motor deficiencies in motor tasks, such as decreased grip strength and performance on the raised beam task (Heck et al., 2008), and higher latency to fall on the rotarod test (Sun et al., 2015). The loss of maternal UBE3A in the adult Ube3a m-/p+ AS mouse model affects Ldhb protein expression in the cerebellum but not in the hippocampus. This suggests that the absence of maternal UBE3A may specifically influence the expression of specific metabolic proteins in the cerebellum. Observations suggest lactate may increase during early development in AS mice (Gupta et al., 2024), possibly affecting LDHs and MCTs in adulthood. These studies contribute to our understanding of lactate metabolism in AS and highlighting the need for continued research given the limited number of reports in this field.
","references":[{"reference":"Bird L. 2014. Angelman syndrome: review of clinical and molecular aspects. The Application of Clinical Genetics : 93.
","pubmedId":"","doi":"10.2147/TACG.S57386 "},{"reference":"Dagli AI, Mathews J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2021 Apr 22]. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1144/
","pubmedId":"","doi":""},{"reference":"Gupta PK, Barak S, Feuermann Y, Goobes G, Kaphzan H. 2024. 1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. Molecular Autism 15: 10.1186/s13229-024-00608-2.
","pubmedId":"","doi":"10.1186/s13229-024-00608-2"},{"reference":"Heck DH, Zhao Y, Roy S, LeDoux MS, Reiter LT. 2008. Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors. Human Molecular Genetics 17: 2181-2189.
","pubmedId":"","doi":"10.1093/hmg/ddn117"},{"reference":"Hoshino D, Setogawa S, Kitaoka Y, Masuda H, Tamura Y, Hatta H, Yanagihara D. 2016. Exercise-induced expression of monocarboxylate transporter 2 in the cerebellum and its contribution to motor performance. Neuroscience Letters 633: 1-6.
","pubmedId":"","doi":"10.1016/j.neulet.2016.09.012"},{"reference":"Kim Y, Dube SE, Park CB. 2025. Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis. The Korean Journal of Physiology & Pharmacology 29: 1-8.
","pubmedId":"","doi":"10.4196/kjpp.24.388"},{"reference":"Leader G, Gilligan R, Whelan S, Coyne R, Caher A, White K, et al., Mannion. 2022. Relationships between challenging behavior and gastrointestinal symptoms, sleep problems, and internalizing and externalizing symptoms in children and adolescents with Angelman syndrome. Research in Developmental Disabilities 128: 104293.
","pubmedId":"","doi":"10.1016/j.ridd.2022.104293"},{"reference":"Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., et al., Yu, T. (2022). Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy, 7 (1), 305. Article 36050306. https://doi.org/10.1038%2Fs41392-022-01151-3
","pubmedId":"","doi":"10.1038%2Fs41392-022-01151-3"},{"reference":"Liu L, MacKenzie KR, Putluri N, Maletić-Savatić M, Bellen HJ. 2017. The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D. Cell Metabolism 26: 719-737.e6.
","pubmedId":"","doi":"10.1016/j.cmet.2017.08.024"},{"reference":"Lu WT, Sun SQ, Li Y, Xu SY, Gan SW, Xu J, et al., Huang. 2018. Curcumin Ameliorates Memory Deficits by Enhancing Lactate Content and MCT2 Expression in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease. The Anatomical Record 302: 332-338.
","pubmedId":"","doi":"10.1002/ar.23969"},{"reference":"Medel, V., Crossley, N., Gajardo, I., Muller, E., Barros, L.F., Shine, J.M., & Sierralta, J. (2022). Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function. Proceedings of the National Academy of Sciences of the United States of America, 119 (33). Article 2204619119. https://doi.org/10.1073%2Fpnas.2204619119
","pubmedId":"","doi":"10.1073%2Fpnas.2204619119"},{"reference":"Pierre K, Pellerin L. 2005. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. Journal of Neurochemistry 94: 1-14.
","pubmedId":"","doi":"10.1111/j.1471-4159.2005.03168.x"},{"reference":"Simchi L, Panov J, Morsy O, Feuermann Y, Kaphzan H. 2020. Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation. Journal of Clinical Medicine 9: 1573.
","pubmedId":"","doi":"10.3390/jcm9051573"},{"reference":"Sun AX, Yuan Q, Fukuda M, Yu W, Yan H, Lim GGY, et al., Je. 2019. Potassium channel dysfunction in human neuronal models of Angelman syndrome. Science 366: 1486-1492.
","pubmedId":"","doi":"10.1126/science.aav5386"},{"reference":"Sun J, Liu Y, Moreno S, Baudry M, Bi X. 2015. Imbalanced Mechanistic Target of Rapamycin C1 and C2 Activity in the Cerebellum of Angelman Syndrome Mice Impairs Motor Function. The Journal of Neuroscience 35: 4706-4718.
","pubmedId":"","doi":"10.1523/JNEUROSCI.4276-14.2015"},{"reference":"Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. 2011. Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation. Cell 144: 810-823.
","pubmedId":"","doi":"10.1016/j.cell.2011.02.018"},{"reference":"Wang J, Cui Y, Yu Z, Wang W, Cheng X, Ji W, et al., Yang. 2019. Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis. Cell Stem Cell 25: 754-767.e9.
","pubmedId":"","doi":"10.1016/j.stem.2019.09.009 "}],"title":"Lactate Dehydrogenase B Expression in Cerebellum of Adult Ube3a m-/p+ Mice
","reviews":[],"curatorReviews":[]}]}},"species":{"species":[{"value":"acer saccharum","label":"Acer saccharum","imageSrc":"","imageAlt":"","mod":"TreeGenes","modLink":"https://treegenesdb.org","linkVariable":""},{"value":"achillea millefolium","label":"Achillea millefolium","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"acinetobacter baylyi","label":"Acinetobacter baylyi","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"actinobacteria bacterium","label":"Actinobacteria bacterium","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"adelges tsugae","label":"Adelges tsugae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"adenocaulon chilense","label":"Adenocaulon chilense","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"aedes japonicus","label":"Aedes japonicus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"aegorhinus vitulus","label":"Aegorhinus vitulus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"alaimidae","label":"Alaimidae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"allobates femoralis","label":"Allobates femoralis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"alnus glutinosa","label":"Alnus glutinosa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"alosa aestivalis","label":"Alosa aestivalis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"alosa pseudoharengus","label":"Alosa pseudoharengus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"alternaria alternata","label":"Alternaria alternata","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"amynthas agrestis","label":"Amynthas Agrestis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ancylostoma caninum","label":"Ancylostoma caninum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ancylostoma ceylanicum","label":"Ancylostoma ceylanicum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"anemone multifida","label":"Anemone multifida","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"anguilla rostrata","label":"Anguilla rostrata","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"anisakis simplex","label":"Anisakis simplex","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"anomala albopilosa","label":"Anomala albopilosa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"anthomyiidae sp","label":"Anthomyiidae sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"anthomyiidae sp","label":"Anthomyiidae sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"arabidopsis","label":"Arabidopsis","imageSrc":"arabidopsis.png","imageAlt":"Arabidopsis graphic by Zoe Zorn CC BY 4.0","mod":"TAIR","modLink":"https://arabidopsis.org","linkVariable":""},{"value":"architeuthis dux","label":"Architeuthis dux","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"arion vulgaris","label":"Arion vulgaris","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"armeria","label":"Armeria","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"artemia","label":"Artemia","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"arthrobacter sp.","label":"Arthrobacter sp.","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ascaridia","label":"Ascaridia","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ascaridia galli","label":"Ascaridia galli","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"asparagopsis taxiformis","label":"Asparagopsis taxiformis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"astatotilapia burtoni","label":"Astatotilapia burtoni","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"avena sativa","label":"Avena sativa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"aves","label":"Aves","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bacillus","label":"Bacillus (firmicutes)","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bacillus cereus","label":"Bacillus cereus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bacillus mycoides","label":"Bacillus mycoides","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bacillus subtilis","label":"Bacillus subtilis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bacillus thuringiensis","label":"Bacillus thuringiensis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bacillus toyonensis","label":"Bacillus toyonensis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bacillus wiedmannii","label":"Bacillus wiedmannii","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bacteria","label":"Bacteria","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bacteriophage","label":"Bacteriophage","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bactrocera","label":"Bactrocera sp.","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"batrachospermum gelatinosum","label":"Batrachospermum gelatinosum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"betula lenta","label":"Betula lenta","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"betula nigra","label":"Betula nigra","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bombus dahlbohmii","label":"Bombus dahlbohmii","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bombus terrestris","label":"Bombus terrestris","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bombyx mori","label":"Bombyx mori","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bos taurus","label":"Bos Taurus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"brachygobius doriae","label":"Brachygobius doriae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"brassica oleracea","label":"Brassica oleracea","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"brassica rapa","label":"Brassica rapa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"brugia malayi","label":"Brugia malayi","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"burkholderia thailandensis","label":"Burkholderia thailandensis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"buttiauxella","label":"Buttiauxella","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"caenorhabditis brenneri","label":"Caenorhabditis brenneri","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"caenorhabditis briggsae","label":"Caenorhabditis briggsae","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"c. elegans","label":"Caenorhabditis elegans","imageSrc":"c-elegans.jpg","imageAlt":"C. elegans graphic by Zoe Zorn CC BY 4.0","mod":"WormBase","modLink":"https://wormbase.org","linkVariable":""},{"value":"caenorhabditis inopinata","label":"Caenorhabditis inopinata","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"caenorhabditis japonica","label":"Caenorhabditis japonica","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"caenorhabditis nigoni","label":"Caenorhabditis nigoni","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"caenorhabditis remanei","label":"Caenorhabditis remanei","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"caenorhabditis tropicalis","label":"Caenorhabditis tropicalis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"calidifontibacillus","label":"Calidifontibacillus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"calidifontibacillus erzuremensis","label":"Calidifontibacillus erzuremensis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"calliphora sp","label":"Calliphora sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"caltha sagittata","label":"Caltha sagittata","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"cambarus latimanus","label":"Cambarus latimanus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"candida albicans","label":"Candida albicans","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"canis familiaris","label":"Canis familiaris","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"cannabis sativa","label":"Cannabis sativa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"caretta caretta","label":"Caretta caretta","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"cassiopea xamachana","label":"Cassiopea xamachana","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"caulobacter vibrioides","label":"Caulobacter vibrioides","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"cephalopods","label":"Cephalopoda","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"cerastium arvense","label":"Cerastium arvense","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ceriodaphnia","label":"Ceriodaphnia","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ceroglossus suturalis","label":"Ceroglossus suturalis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"chaetoceros","label":"Chaetoceros","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"chamaecrista fasciculata","label":"Chamaecrista fasciculata","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"chilicola chalcidiformis","label":"Chilicola chalcidiformis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"chitinimonas","label":"Chitinimonas","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"chlamydomonas reinhardtii","label":"Chlamydomonas reinhardtii","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"chromobacterium","label":"Chromobacterium","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"chrysemys picta","label":"Chrysemys picta","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"chrysoperla rufilabris","label":"Chrysoperla rufilabris","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"citrus","label":"Citrus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"clavibacter sp.","label":"Clavibacter sp.","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"colinus virginianus","label":"Colinus virginianus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"crassostrea virginica","label":"Crassostrea virginica","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"crithidia fasciculata","label":"Crithidia fasciculata","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"cutibacterium acnes","label":"Cutibacterium acnes","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"cyanobacteria","label":"Cyanobacteria","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"daphnia","label":"Daphnia","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"daphnia pulex","label":"Daphnia pulex","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"diabrotica virgifera","label":"Diabrotica virgifera","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"diabrotica virgifera virgifera virus 1","label":"Diabrotica virgifera virgifera virus 1","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"d. discoideum","label":"Dictyostelium discoideum","imageSrc":"dicty.png","imageAlt":"D. discoideum","mod":"dictyBase","modLink":"http://dictybase.org","linkVariable":""},{"value":"diptera","label":"Diptera","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"dotocryptus bellicosus","label":"Dotocryptus bellicosus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"drechmeria coniospora","label":"Drechmeria coniospora","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"drosophila","label":"Drosophila","imageSrc":"drosophila.png","imageAlt":"Drosophila graphic by Zoe Zorn CC BY 4.0","mod":"FlyBase","modLink":"https://flybase.org/doi/","linkVariable":"doi"},{"value":"dryopteris campyloptera","label":"Dryopteris campyloptera","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"dryopteris expansa","label":"Dryopteris expansa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"dryopteris intermedia","label":"Dryopteris intermedia","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"dugesia dorotocephala","label":"Dugesia dorotocephala","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"elasmobranchii","label":"Elasmobranchii","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"embryophyta","label":"Embryophyta","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"enoploteuthis chunii","label":"Enoploteuthis chunii","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"enterobacter aerogenes","label":"Enterobacter aerogenes","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"enterococcus raffinosus","label":"Enterococcus raffinosus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"epichloë coenophiala","label":"Epichloë coenophiala","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"equus caballus","label":"Equus caballus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"erigeron sp","label":"Erigeron sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"eristalis","label":"Eristalis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"eruca vesicaria","label":"Eruca vesicaria","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"erwinia carotovora","label":"Erwinia carotovora","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"erythronium americanum","label":"Erythronium americanum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"escherichia coli","label":"Escherichia coli","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"eukaryota","label":"Eukaryotes","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"felis catus","label":"Felis catus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"francisella novicida","label":"Francisella novicida","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"francisella tularensis","label":"Francisella tularensis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"fraxinus americana","label":"Fraxinus americana","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"fucus distichus","label":"Fucus distichus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"fungi","label":"Fungi","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"gasteropelecus sp.","label":"Gasteropelecus sp.","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"geranium sp","label":"Geranium sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"girardia","label":"Girardia","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"glaucomys volans","label":"Glaucomys volans","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"glycine max","label":"Glycine max","imageSrc":"","imageAlt":"","mod":"Soybase","modLink":"https://soybase.org","linkVariable":""},{"value":"glyptemys insculpta","label":"Glyptemys insculpta","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"gossypium hirsutum","label":"Gossypium hirsutum","imageSrc":"","imageAlt":"","mod":"CottonGen","modLink":"https://www.cottongen.org/","linkVariable":""},{"value":"gromphadorhina portentosa","label":"Gromphadorhina portentosa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"gryllodes sigillatus","label":"Gryllodes sigillatus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"haliotis rufescens","label":"Haliotis rufescens","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"hepacivirus hominis","label":"Hepatitis C Virus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"herpes simplex virus type 1","label":"Herpes simplex virus type 1","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"human","label":"Human","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"human coronavirus oc43","label":"Human coronavirus OC43","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"hydra vulgaris","label":"Hydra vulgaris","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"hydropsyche sp","label":"Hydropsyche sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"hymenoptera","label":"Hymenoptera","imageSrc":"","imageAlt":"","mod":"Hymenoptera Genome Database","modLink":"https://hymenoptera.elsiklab.missouri.edu/","linkVariable":""},{"value":"hypochaeris radicata","label":"Hypochaeris radicata","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"hypodynerus vespiformis","label":"Hypodynerus vespiformis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"iflaviridae","label":"Iflaviridae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"iflavuris","label":"Iflavirus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ipomoea hederacea","label":"Ipomoea hederacea","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ischnomera","label":"Ischnomera","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ischnomera ruficollis","label":"Ischnomera ruficollis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"julidochromis marlieri","label":"Julidochromis marlieri","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"juniperus virginiana","label":"Juniperus virginiana","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"kluyveromyces marxianus","label":"Kluyveromyces marxianus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"l. casei","label":"L. casei","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"lacticaseibacillus casei","label":"Lacticaseibacillus casei","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"larentiinae sp","label":"Larentiinae sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"laurus nobilis","label":"Laurus nobilis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"lepidoptera","label":"Lepidoptera","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"leucanthemum vulgare","label":"Leucanthemum vulgare","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"linepithema humile","label":"Linepithema humile","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"liometopum occidentale","label":"Liometopum occidentale","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"lolium arundinaceum","label":"Lolium arundinaceum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"lumbriculus variegatus","label":"Lumbriculus variegatus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"lumbricus terrestris","label":"Lumbricus terrestris","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"lupinus polyphyllus","label":"Lupinus polyphyllus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"lycorma delicatula","label":"Lycorma delicatula","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"lynx rufus","label":"Lynx rufus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"magnaporthe oryzae","label":"Magnaporthe oryzae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"mammalia","label":"Mammalia","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"manihot esculenta","label":"Manihot esculenta","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"medicago lupulina","label":"Medicago lupulina","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"meloidogyne","label":"Meloidogyne","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"mimus polyglottos","label":"Mimus polyglottos","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"bryophyta","label":"Mosses","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"mouse","label":"Mouse","imageSrc":"","imageAlt":"","mod":"MGI","modLink":"https://informatics.jax.org","linkVariable":""},{"value":"m. minutoides","label":"Mus minutoides","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"mycobacterium smegmatis","label":"Mycobacterium smegmatis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"nakaseomyces glabratus","label":"Nakaseomyces glabratus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"nauphoeta cinerea","label":"Nauphoeta cinerea","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"neurospora","label":"Neurospora","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"n. benthamiana","label":"Nicotiana benthamiana","imageSrc":"","imageAlt":"","mod":"Solgenomics Network","modLink":"https://solgenomics.net/organism/Nicotiana_benthamiana/genome","linkVariable":""},{"value":"nicotiana tabacum","label":"Nicotiana tabacum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"noctuidae","label":"Noctuidae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"noctuidae sp","label":"Noctuidae sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"nothobranchius furzeri","label":"Nothobranchius furzeri","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"onchocerca volvulus","label":"Onchocerca volvulus","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"orconectes virilis","label":"Orconectes virilis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ormia ochracea","label":"Ormia ochracea","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"o. sativa","label":"Oryza sativa","imageSrc":"","imageAlt":"","mod":"Gramene","modLink":"https://www.gramene.org/","linkVariable":""},{"value":"other","label":"Other","imageSrc":"","imageAlt":"","mod":null,"modLink":null,"linkVariable":null},{"value":"oxalis enneaphylla","label":"Oxalis enneaphylla","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"paenarthrobacter nicotinovorans","label":"Paenarthrobacter nicotinovorans","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"paenarthrobacter nicotinovorans","label":"Paenarthrobacter nicotinovorans","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pantoea","label":"Pantoea","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pantoea agglomerans","label":"Pantoea agglomerans","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"papaver sp","label":"Papaver sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"paramecium bursaria","label":"Paramecium bursaria","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"partitiviridae","label":"Partitiviridae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pelodiscus sinensis","label":"Pelodiscus sinensis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"perezia recurvata","label":"Perezia recurvata","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"petromyzon marinus","label":"Petromyzon marinus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"photinus pyralis","label":"Photinus pyralis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"photinus pyralis associated partiti-like virus","label":"Photinus pyralis associated partiti-like virus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"photinus pyralis iflavirus 1","label":"Photinus pyralis iflavirus 1","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"physcomitrium patens","label":"Physcomitrium patens","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pinus strobus","label":"Pinus strobus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pinus taeda","label":"Pinus taeda","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"platycheirus","label":"Platycheirus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"plectus sambesii","label":"Plectus sambesii","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pogonomyrmex occidentalis","label":"Pogonomyrmex occidentalis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"poncirus trifoliata","label":"Poncirus trifoliata","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"populus deltoides","label":"Populus deltoides","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"potato virus y","label":"Potato virus Y","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"primula magellanica","label":"Primula magellanica","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pristionchus pacificus","label":"Pristionchus pacificus","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"prunus persica","label":"Prunus persica","imageSrc":"","imageAlt":"","mod":"Genome Database for Rosaceae","modLink":"https://www.rosaceae.org/","linkVariable":""},{"value":"psalmopoeus iriminia","label":"Psalmopoeus iriminia","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pseudanabaena sp.","label":"Pseudanabaena sp.","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pseudomonas","label":"Pseudomonas","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pseudomonas aeruginosa","label":"Pseudomonas aeruginosa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pseudomonas glycinae","label":"Pseudomonas glycinae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pseudomonas putida","label":"Pseudomonas putida","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pseudomonas syringae","label":"Pseudomonas syringae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"pterophyllum scalare","label":"Pterophyllum scalare","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"python regius","label":"Python regius","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"quercus macrocarpa","label":"Quercus macrocarpa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ralstonia solanacearum","label":"Ralstonia solanacearum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ranitomeya imitator","label":"Ranitomeya imitator","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ranunculus peduncularis","label":"Ranunculus peduncularis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"rat","label":"Rat","imageSrc":"","imageAlt":"","mod":"RGD","modLink":"https://rgd.mcw.edu","linkVariable":""},{"value":"rheinheimera","label":"Rheinheimera","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ribes rubrum","label":"Ribes rubrum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"sars-cov-2","label":"SARS-CoV-2","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"s. cerevisiae","label":"Saccharomyces cerevisiae","imageSrc":"yeast.png","imageAlt":"Yeast graphic by Zoe Zorn CC BY 4.0","mod":"SGD","modLink":"https://yeastgenome.org","linkVariable":""},{"value":"saccharomyces paradoxus","label":"Saccharomyces paradoxus ","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"s. uvarum","label":"Saccharomyces uvarum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"schistosoma","label":"Schistosoma","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"schizosaccharomyces japonicus","label":"Schizosaccharomyces japonicus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"s. pombe","label":"Schizosaccharomyces pombe","imageSrc":"pombe.png","imageAlt":"Pombe graphic by Zoe Zorn © Caltech","mod":"PomBase","modLink":"https://www.pombase.org/reference/PMID:","linkVariable":"pmId"},{"value":"schmidtea mediterranea","label":"Schmidtea mediterranea","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"senecio sp","label":"Senecio sp","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"simocephalus","label":"Simocephalus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"siraitia grosvenorii","label":"Siraitia grosvenorii","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"solanum lycopersicum","label":"Solanum lycopersicum","imageSrc":"","imageAlt":"","mod":"Solgenomics Network","modLink":"https://solgenomics.net/organism/1/view/","linkVariable":""},{"value":"sorghum","label":"Sorghum","imageSrc":"","imageAlt":"","mod":"SorghumBase","modLink":"https://www.sorghumbase.org","linkVariable":""},{"value":"spiroplasma eriocheiris","label":"Spiroplasma eriocheiris","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"staphylococcus aureus","label":"Staphylococcus aureus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"staphylococcus epidermidis","label":"Staphylococcus epidermidis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"steinernema carpocapsae","label":"Steinernema carpocapsae","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"https://wormbase.org","linkVariable":""},{"value":"steinernema hermaphroditum","label":"Steinernema hermaphroditum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"stenotrophomonas geniculata","label":"Stenotrophomonas geniculata","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"streptococcus gordonii ","label":"Streptococcus gordonii ","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"streptococcus mutans","label":"Streptococcus mutans","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":" streptococcus pneumoniae","label":"Streptococcus pneumoniae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"s. purpuratus","label":"Strongylocentrotus purpuratus","imageSrc":"","imageAlt":"","mod":"Echinobase","modLink":"https://www.echinobase.org","linkVariable":""},{"value":"strongyloides ratti","label":"Strongyloides ratti","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"sulfolobus","label":"Sulfolobus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"symphoricarpos albus","label":"Symphoricarpos albus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"syncirsodes","label":"Syncirsodes","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"synechococcus elongatus","label":"Synechococcus elongatus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"syrphidae","label":"Syrphidae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"tarantobelus jeffdanielsi","label":"Tarantobelus jeffdanielsi","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"taraxacum officinale","label":"Taraxacum officinale","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"tatochila theodice","label":"Tatochila theodice","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"tetrahymena","label":"Tetrahymena","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"tetramorium immigrans","label":"Tetramorium immigrans","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"tomato brown rugose fruit virus","label":"ToBRFV","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"trachemys scripta","label":"Trachemys scripta","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"tribolium castaneum","label":"Tribolium castaneum","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"trichoptera","label":"Trichoptera","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"trichuris muris","label":"Trichuris muris","imageSrc":"","imageAlt":"","mod":"WormBase","modLink":"www.wormbase.org","linkVariable":""},{"value":"trifolium repens","label":"Trifolium repens","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"trypoxylus dichotomus","label":"Trypoxylus dichotomus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"tsuga canadensis","label":"Tsuga canadensis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"ulva expansa","label":"Ulva expansa","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"universal","label":"Universal","imageSrc":"","imageAlt":"","mod":null,"modLink":null,"linkVariable":null},{"value":"vargula hilgendorfii","label":"Vargula hilgendorfii","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"vespula vulgaris","label":"Vespula vulgaris","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"virus","label":"Virus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"watasenia scintillans","label":"Watasenia scintillans","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"wolbachia pipientis","label":"Wolbachia pipientis","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"xenopus","label":"Xenopus","imageSrc":"xenopus.png","imageAlt":"Xenopus graphic by Zoe Zorn CC BY 4.0","mod":"XenBase","modLink":"https://xenbase.org","linkVariable":""},{"value":"xenorhabdus griffiniae","label":"Xenorhabdus griffiniae","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"yramea cytheris","label":"Yramea cytheris","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"zaprionus indianus","label":"Zaprionus indianus","imageSrc":"","imageAlt":"","mod":"","modLink":"","linkVariable":""},{"value":"zea mays","label":"Zea mays","imageSrc":"","imageAlt":"","mod":"MaizeGDB","modLink":"https://www.maizegdb.org","linkVariable":""},{"value":"zebrafish","label":"Zebrafish","imageSrc":"zebrafish.png","imageAlt":"Zebrafish graphic by Zoe Zorn CC BY 4.0","mod":"ZFIN","modLink":"https://zfin.org","linkVariable":""}]}},"pageContext":{"id":"4e272b40-2f73-4e40-8368-72f50715926d","citedBy":[],"parsedCsv":{"csvHeader":[],"csvData":[]}}}, "staticQueryHashes": ["2114697108"]}