Usp46, encoding a ubiquitin specific peptidase, is a quantitative trait gene underlying "behavioral despair" in mice

Shizufumi Ebihara, Shigeru Tomida, Takayoshi Mamiya, Hirotake Sakamaki, Masami Miura, Toshihiko Aosaki, Masao Masuda, Minae Niwa, Tsutomu Kameyama, Junya Kobayashi, Yuka Iwaki, Saki Imai, Akira Ishikawa, Kuniya Abe, Takashi Yoshimura, Toshitaka Nabeshima

研究成果: ジャーナルへの寄稿総説査読


CS mice exhibit several distinct phenotypes of circadian behavioral rhythms and sleep properties. Because many mental illnesses are associated with abnormalities in the circadian rhythms and sleep pattern, we characterized the behavioral phenotypes in CS mice with a battery of behavioral tests. Among these phenotypes, we found that CS mice exhibit an extremely low immobility time in both the tail suspension test (TST) and forced swimming test (FST). To uncover the genetic basis for lower immobility time, we first performed quantitative trait locus (QTL) mapping using CS and C57BL/6J mice, which revealed significant QTLs on chromosomes (Chrs) 4 (FST) and 5 (TST and FST). To identify the quantitative trait gene on Chr 5, we narrowed the QTL interval to 0.5 Mb using several congenic and subcongenic strains. Ubiquitin-specific peptidase 46 (Usp46) with a lysine codon deletion was located in this region. This deletion affected nest-building, muscimol-induced righting reflex, and anti-immobility effects of imipramine. The muscimol-induced current in the hippocampal CA1 pyramidal neurons and hippocampal expression of the 67-kDa isoform of glutamic acid decarboxylase significantly decreased in Usp46 mutant mice. All these phenotypes were rescued in transgenic mice with bacterial artificial chromosomes containing wild-type Usp46. Thus, Usp46 affects the immobility in the TST and FST, and it is implicated in the regulation of GABA action.

ジャーナルSleep and Biological Rhythms
出版ステータス出版済み - 04-2010

All Science Journal Classification (ASJC) codes

  • 生理学
  • 神経心理学および生理心理学
  • 神経学
  • 生理学(医学)


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