Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests.
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.
Tomida
Shigeru
S
Division of Biomodeling, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.
Mamiya
Takayoshi
T
Sakamaki
Hirotake
H
Miura
Masami
M
Aosaki
Toshihiko
T
Masuda
Masao
M
Niwa
Minae
M
Kameyama
Tsutomu
T
Kobayashi
Junya
J
Iwaki
Yuka
Y
Imai
Saki
S
Ishikawa
Akira
A
Abe
Kuniya
K
Yoshimura
Takashi
T
Nabeshima
Toshitaka
T
Ebihara
Shizufumi
S
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
D003062:Codon; D005680:gamma-Aminobutyric Acid; D010450:Endopeptidases; C091939:ubiquitin isopeptidase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1