Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder

Kevin C Davis; Kenji Saito; Samuel R Rodeghiero; Brandon A Toth; Michael Lutter; Huxing Cui

doi:10.3389/fnins.2020.00139

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Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder

Journal article

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Peer reviewed

Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder

Kevin C Davis, Kenji Saito, Samuel R Rodeghiero, Brandon A Toth, Michael Lutter and Huxing Cui

Frontiers in neuroscience, Vol.14, 139

02/21/2020

DOI: 10.3389/fnins.2020.00139

PMCID: PMC7046559

PMID: 32153359

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Abstract

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 (HDAC4 A786T ) 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 Hdac4 A778T (corresponding to human HDAC4 A786T ) 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 Hdac4 A778T 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 Hdac4 A778T mutation in affecting mouse behaviors. Homozygous Hdac4 A778T mice could therefore be a useful animal model to gain insight into the neurobiological basis of EDs.

Eating Disorders

Neuroscience

mouse behaviors

body weight

social subordination

humanized mouse model

genetic mutation

histone deacetylase 4

food intake

Details

Title: Subtitle: Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder
Creators: Kevin C Davis - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine
Kenji Saito - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine
Samuel R Rodeghiero - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine
Brandon A Toth - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine
Michael Lutter - Eating Recovery Center of San Antonio
Huxing Cui - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine
Resource Type: Journal article
Publication Details: Frontiers in neuroscience, Vol.14, 139
DOI: 10.3389/fnins.2020.00139
PMID: 32153359
PMCID: PMC7046559
NLM abbreviation: Front Neurosci
ISSN: 1662-4548
eISSN: 1662-453X
Publisher: Frontiers Media S.A
Language: English
Date published: 02/21/2020
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984070962202771

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