title: Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests.
abstract: The tail suspension test (TST) and forced swimming test (FST) are widely used for assessing antidepressant activity and depression-like behavior. We found that CS mice show negligible immobility in inescapable situations. Quantitative trait locus (QTL) mapping using CS and C57BL/6J mice revealed significant QTLs on chromosomes 4 (FST) and 5 (TST and FST). To identify the quantitative trait gene on chromosome 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 were significantly decreased in the Usp46 mutant mice compared to control mice. 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.
authors.affiliation: Division of Biomodeling, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tomida
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Mamiya
authors.forename: Hirotake
authors.initials: H
authors.lastname: Sakamaki
authors.forename: Masami
authors.initials: M
authors.lastname: Miura
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Aosaki
authors.forename: Masao
authors.initials: M
authors.lastname: Masuda
authors.forename: Minae
authors.initials: M
authors.lastname: Niwa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kameyama
authors.forename: Junya
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Iwaki
authors.forename: Saki
authors.initials: S
authors.lastname: Imai
authors.forename: Akira
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Kuniya
authors.initials: K
authors.lastname: Abe
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.forename: Shizufumi
authors.initials: S
authors.lastname: Ebihara
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003062:Codon / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics; D056726:Genetic Association Studies / Q000379:methods; D005968:Glutamate Decarboxylase / Q000235:genetics; D007103:Immobilization; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008815:Mice, Inbred Strains / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D017384:Sequence Deletion; D013623:Tail / Q000033:anatomy & histology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid
chemical_list: D003062:Codon; D005680:gamma-Aminobutyric Acid; D010450:Endopeptidases; C091939:ubiquitin isopeptidase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1