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

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
Pages (from-to)114-119
Number of pages6
JournalSleep and Biological Rhythms
Volume8
Issue number2
DOIs
Publication statusPublished - 01-04-2010
Externally publishedYes

Fingerprint

Ubiquitin
Hindlimb Suspension
Peptide Hydrolases
Phenotype
Muscimol
Quantitative Trait Loci
Circadian Rhythm
Genes
Sleep
Righting Reflex
Bacterial Artificial Chromosomes
Chromosomes, Human, Pair 4
Glutamate Decarboxylase
Pyramidal Cells
Imipramine
Inbred C57BL Mouse
Codon
gamma-Aminobutyric Acid
Transgenic Mice
Lysine

All Science Journal Classification (ASJC) codes

  • Physiology
  • Neuropsychology and Physiological Psychology
  • Neurology
  • Physiology (medical)

Cite this

Ebihara, Shizufumi ; Tomida, Shigeru ; Mamiya, Takayoshi ; Sakamaki, Hirotake ; Miura, Masami ; Aosaki, Toshihiko ; Masuda, Masao ; Niwa, Minae ; Kameyama, Tsutomu ; Kobayashi, Junya ; Iwaki, Yuka ; Imai, Saki ; Ishikawa, Akira ; Abe, Kuniya ; Yoshimura, Takashi ; Nabeshima, Toshitaka. / Usp46, encoding a ubiquitin specific peptidase, is a quantitative trait gene underlying "behavioral despair" in mice. In: Sleep and Biological Rhythms. 2010 ; Vol. 8, No. 2. pp. 114-119.
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Ebihara, S, Tomida, S, Mamiya, T, Sakamaki, H, Miura, M, Aosaki, T, Masuda, M, Niwa, M, Kameyama, T, Kobayashi, J, Iwaki, Y, Imai, S, Ishikawa, A, Abe, K, Yoshimura, T & Nabeshima, T 2010, 'Usp46, encoding a ubiquitin specific peptidase, is a quantitative trait gene underlying "behavioral despair" in mice', Sleep and Biological Rhythms, vol. 8, no. 2, pp. 114-119. https://doi.org/10.1111/j.1479-8425.2010.00435.x

Usp46, encoding a ubiquitin specific peptidase, is a quantitative trait gene underlying "behavioral despair" in mice. / Ebihara, Shizufumi; Tomida, Shigeru; Mamiya, Takayoshi; Sakamaki, Hirotake; Miura, Masami; Aosaki, Toshihiko; Masuda, Masao; Niwa, Minae; Kameyama, Tsutomu; Kobayashi, Junya; Iwaki, Yuka; Imai, Saki; Ishikawa, Akira; Abe, Kuniya; Yoshimura, Takashi; Nabeshima, Toshitaka.

In: Sleep and Biological Rhythms, Vol. 8, No. 2, 01.04.2010, p. 114-119.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Usp46, encoding a ubiquitin specific peptidase, is a quantitative trait gene underlying "behavioral despair" in mice

AU - Ebihara, Shizufumi

AU - Tomida, Shigeru

AU - Mamiya, Takayoshi

AU - Sakamaki, Hirotake

AU - Miura, Masami

AU - Aosaki, Toshihiko

AU - Masuda, Masao

AU - Niwa, Minae

AU - Kameyama, Tsutomu

AU - Kobayashi, Junya

AU - Iwaki, Yuka

AU - Imai, Saki

AU - Ishikawa, Akira

AU - Abe, Kuniya

AU - Yoshimura, Takashi

AU - Nabeshima, Toshitaka

PY - 2010/4/1

Y1 - 2010/4/1

N2 - 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.

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