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

Frontiers in Neuroscience
Kevin C DavisHuxing Cui

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 behav...Continue Reading

References

Dec 12, 2002·Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie·A KarwautzM H Friedrich
Oct 28, 2003·Psychology and Psychotherapy·Nicholas A TroopMelanie Katzman
Jul 30, 2005·Molecular Endocrinology·Hoyee LeongGeoffrey L Greene
Jul 5, 2007·The International Journal of Eating Disorders·Frances ConnanJanet Treasure
May 24, 2008·Developmental Neurobiology·Nazanin MajdzadehSantosh R D'Mello
Jun 24, 2008·Eating Disorders·Nicholas A Troop, Anna H Baker
Sep 22, 2009·Journal of Psychiatric Research·Teruyuki HobaraYoshifumi Watanabe
Oct 17, 2009·The American Journal of Psychiatry·Anne-Katharina FladungJörn von Wietersheim
Oct 5, 2010·Neuroscience and Biobehavioral Reviews·Iain C CampbellUlrike Schmidt
Nov 17, 2010·Molecular Psychiatry·K WangUNKNOWN Price Foundation Collaborative Group
Nov 15, 2011·Current Topics in Behavioral Neurosciences·Owen Carmichael, Samuel Lockhart
Jun 1, 2010·Current Protocols in Pharmacology·Vincent CastagnéRoger D Porsolt
Aug 10, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mi-Sung KimLisa M Monteggia
Jan 10, 2013·Clinical Psychology & Psychotherapy·Nicholas A TroopJanet L Treasure
Nov 13, 2013·The Journal of Clinical Investigation·Huxing CuiMichael Lutter
Dec 19, 2013·PloS One·Helen L FitzsimonsMaxwell J Scott
Feb 12, 2014·Molecular Psychiatry·V BoraskaC M Bulik
Mar 26, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ambalika SarkarVidita A Vaidya
May 28, 2014·Neuropathology and Applied Neurobiology·Amy WhitehouseDavid M A Mann
Jul 1, 2014·The International Journal of Eating Disorders·Michael StroberHoward Steiger
Mar 12, 2015·Frontiers in Cellular Neuroscience·Michal MielcarekFabien Guidez
Mar 27, 2015·The International Journal of Eating Disorders·Linda BooijHoward Steiger
Apr 14, 2015·Cell Reports·Huxing CuiMichael Lutter
Jul 2, 2016·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Miriam KesselmeierUNKNOWN GCAN and WTCCC3
Jul 8, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Fumihiro HiguchiYoshifumi Watanabe
Nov 26, 2016·Biological Psychiatry·Michael LutterHuxing Cui
May 13, 2017·The American Journal of Psychiatry·Laramie DuncanCynthia M Bulik
May 20, 2017·Advances in Experimental Medicine and Biology·Lea Thaler, Howard Steiger
May 27, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Michael Lutter
Jun 22, 2017·Addiction Biology·Rachel D PenrodChristopher W Cowan
Sep 25, 2017·Current Psychiatry Reports·Jessica H BakerMelissa A Munn-Chernoff
Dec 20, 2017·Psychiatric Genetics·Subha SubramanianJames B Potash

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
PCR
genotyping
electrophoresis

Software Mentioned

LABORAS
Laboratory Animal Behavior Observation Registration and Analys...
maze
ANY
GraphPad Prism
Maze Behavioral tracking

Related Concepts

Related Feeds

Antipsychotic-Induced Weight Gain

Antipsychotic-induced weight gain (aiwg) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. Here are the latest discoveries pertaining to AIWG.