Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder
Eating disorders (EDs) are serious mental illnesses thought to arise from the complex gene-environment interactions. DNA methylation patterns in histone deacetylase 4 (HDAC4) locus have been associated with EDs and we have previously identified a missense mutation in the HDAC4 gene (HDAC4A786T) that...
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| Format: | Article |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2020.00139/full |
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| author | Kevin C. Davis Kenji Saito Samuel R. Rodeghiero Brandon A. Toth Michael Lutter Huxing Cui Huxing Cui Huxing Cui Huxing Cui |
| author_facet | Kevin C. Davis Kenji Saito Samuel R. Rodeghiero Brandon A. Toth Michael Lutter Huxing Cui Huxing Cui Huxing Cui Huxing Cui |
| author_sort | Kevin C. Davis |
| collection | DOAJ |
| description | Eating disorders (EDs) are serious mental illnesses thought to arise from the complex gene-environment interactions. DNA methylation patterns in histone deacetylase 4 (HDAC4) locus have been associated with EDs and we have previously identified a missense mutation in the HDAC4 gene (HDAC4A786T) that increases the risk of developing an ED. In order to evaluate the biological consequences of this variant and establish a useful mouse model of EDs, here we performed behavioral characterization of mice homozygous for Hdac4A778T (corresponding to human HDAC4A786T) that were further backcrossed onto C57BL/6 background. When fed high-fat diet, male, but not female, homozygous mice showed a trend toward decreased weight gain compared to their wild-type littermates. Behaviorally, male, but not female, homozygous mice spent less time in eating and exhibited reduced motivation to work for palatable food and light phase-specific decrease in locomotor activity. Additionally, homozygous Hdac4A778T female, but not male, mice display social subordination when subjected to a tube dominance test. Collectively, these results reveal a complex sex- and circadian-dependent role of ED-associated Hdac4A778T mutation in affecting mouse behaviors. Homozygous Hdac4A778T mice could therefore be a useful animal model to gain insight into the neurobiological basis of EDs. |
| first_indexed | 2024-12-10T23:26:51Z |
| format | Article |
| id | doaj.art-329b5b7dcde84a4ea7f9b23d1c0d6c25 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-10T23:26:51Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-329b5b7dcde84a4ea7f9b23d1c0d6c252022-12-22T01:29:32ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-02-011410.3389/fnins.2020.00139518835Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating DisorderKevin C. Davis0Kenji Saito1Samuel R. Rodeghiero2Brandon A. Toth3Michael Lutter4Huxing Cui5Huxing Cui6Huxing Cui7Huxing Cui8Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesDepartment of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesDepartment of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesDepartment of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesEating Recovery Center of San Antonio, San Antonio, TX, United StatesDepartment of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesF.O.E. Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesObesity Research and Educational Initiative, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesIowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, United StatesEating disorders (EDs) are serious mental illnesses thought to arise from the complex gene-environment interactions. DNA methylation patterns in histone deacetylase 4 (HDAC4) locus have been associated with EDs and we have previously identified a missense mutation in the HDAC4 gene (HDAC4A786T) that increases the risk of developing an ED. In order to evaluate the biological consequences of this variant and establish a useful mouse model of EDs, here we performed behavioral characterization of mice homozygous for Hdac4A778T (corresponding to human HDAC4A786T) that were further backcrossed onto C57BL/6 background. When fed high-fat diet, male, but not female, homozygous mice showed a trend toward decreased weight gain compared to their wild-type littermates. Behaviorally, male, but not female, homozygous mice spent less time in eating and exhibited reduced motivation to work for palatable food and light phase-specific decrease in locomotor activity. Additionally, homozygous Hdac4A778T female, but not male, mice display social subordination when subjected to a tube dominance test. Collectively, these results reveal a complex sex- and circadian-dependent role of ED-associated Hdac4A778T mutation in affecting mouse behaviors. Homozygous Hdac4A778T mice could therefore be a useful animal model to gain insight into the neurobiological basis of EDs.https://www.frontiersin.org/article/10.3389/fnins.2020.00139/fulleating disordershistone deacetylase 4mouse behaviorssocial subordinationbody weightfood intake |
| spellingShingle | Kevin C. Davis Kenji Saito Samuel R. Rodeghiero Brandon A. Toth Michael Lutter Huxing Cui Huxing Cui Huxing Cui Huxing Cui Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder Frontiers in Neuroscience eating disorders histone deacetylase 4 mouse behaviors social subordination body weight food intake |
| title | Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder |
| title_full | Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder |
| title_fullStr | Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder |
| title_full_unstemmed | Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder |
| title_short | Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder |
| title_sort | behavioral alterations in mice carrying homozygous hdac4a778t missense mutation associated with eating disorder |
| topic | eating disorders histone deacetylase 4 mouse behaviors social subordination body weight food intake |
| url | https://www.frontiersin.org/article/10.3389/fnins.2020.00139/full |
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