title: The Eating-Disorder Associated HDAC4A778TMutation Alters Feeding Behaviors in Female Mice.
abstract: While eating disorders (EDs) are thought to result from a combination of environmental and psychological stressors superimposed on genetic vulnerability, the neurobiological basis of EDs remains incompletely understood. We recently reported that a rare missense mutation in the gene for the transcriptional repressor histone deacetylase 4 (HDAC4) is associated with the risk of developing an ED in humans.
  
  
  
  To understand the biological consequences of this missense mutation, we created transgenic mice carrying this mutation by introducing the alanine to threonine mutation at position 778 of mouse Hdac4 (corresponding to position 786 of the human protein). Bioinformatic analysis to identify Hdac4-regulated genes was performed using available databases.
  
  
  
  Male mice heterozygous for HDAC4A778Tdid not show any metabolic or behavioral differences. In contrast, female mice heterozygous for HDAC4A778Tdisplay several ED-related feeding and behavioral deficits depending on housing condition. Individually housed HDAC4A778Tfemale mice exhibit reduced effortful responding for high-fat diet and compulsive grooming, whereas group-housed female mice display increased weight gain on high-fat diet, reduced behavioral despair, and increased anxiety-like behaviors. Bioinformatic analysis identifies mitochondrial biogenesis including synthesis of glutamate/gamma-aminobutyric acid as a potential transcriptional target of HDAC4A778Tactivity relevant to the behavioral deficits identified in this new mouse model of disordered eating.
  
  
  
  The HDAC4A778Tmouse line is a novel model of ED-related behaviors and identifies mitochondrial biogenesis as a potential molecular pathway contributing to behavioral deficits.
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, Iowa.
authors.forename: Michael
authors.initials: M
authors.lastname: Lutter
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, Iowa.
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Khan
authors.affiliation: Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, Iowa.
authors.forename: Kenji
authors.initials: K
authors.lastname: Satio
authors.affiliation: Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, Iowa.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Davis
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, Iowa.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Kidder
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, Iowa.
authors.forename: Latisha
authors.initials: L
authors.lastname: McDaniel
authors.affiliation: Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, Iowa.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Darbro
authors.affiliation: Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, Iowa; Neurology, University of Iowa, Carver College of Medicine, Iowa City, Iowa; Free Radical and Radiation Biology, University of Iowa, Carver College of Medicine, Iowa City, Iowa.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Pieper
authors.affiliation: Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, Iowa. Electronic address: Huxing-Cui@uiowa.edu.
authors.forename: Huxing
authors.initials: H
authors.lastname: Cui
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D019295:Computational Biology; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000502:physiology*; D001068:Feeding and Eating Disorders / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006655:Histone Deacetylases / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D020125:Mutation, Missense
chemical_list: C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases
keywords: Anorexia nervosa; Behavior; Eating disorders; Estrogen-related receptor alpha; Feeding; Histone deacetylase 4