title: Behavioral and gene expression analyses of Wfs1 knockout mice as a possible animal model of mood disorder.
abstract: Wolfram disease is a rare genetic disorder frequently accompanying depression and psychosis. Non-symptomatic mutation carriers also have higher rates of depression and suicide. Because WfS1, the causative gene of Wolfram disease, is located at 4p16, a linkage locus for bipolar disorder, mutations of WfS1 were suggested to be involved in the pathophysiology of bipolar disorder. In this study, we performed behavioral and gene expression analyses of Wfs1 knockout mice to assess the validity as an animal model of mood disorder. In addition, the distribution of Wfs1 protein was examined in mouse brain. Wfs1 knockout mice did not show abnormalities in circadian rhythm and periodic fluctuation of wheel-running activity. Behavioral analysis showed that Wfs1 knockout mice had retardation in emotionally triggered behavior, decreased social interaction, and altered behavioral despair depending on experimental conditions. Wfs1-like immunoreactivity in mouse brain showed a similar distribution pattern to that in rats, including several nuclei potentially relevant to the symptoms of mood disorders. Gene expression analysis showed down-regulation of Cdc42ep5 and Rnd1, both of which are related to Rho GTPase, which plays a role in dendrite development. These findings may be relevant to the mood disorder observed in patients with Wolfram disease.
authors.affiliation: Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Hirosawa 2-1, Wako, Saitama 351-0198, Japan. kato@brain.riken.jp
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
authors.forename: Mizuho
authors.initials: M
authors.lastname: Ishiwata
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamada
authors.forename: Takaoki
authors.initials: T
authors.lastname: Kasahara
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kakiuchi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwamoto
authors.forename: Koki
authors.initials: K
authors.lastname: Kawamura
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Ishihara
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D019964:Mood Disorders / Q000235:genetics* / Q000503:physiopathology*; D009043:Motor Activity / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014929:Wolfram Syndrome / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein