RRC ID 4750
Author 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, Ebihara S.
Title Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests.
Journal Nat Genet
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.
Volume 41(6)
Pages 688-95
Published 2009-6-1
DOI 10.1038/ng.344
PII ng.344
PMID 19465912
MeSH Animals Chromosome Mapping Codon / genetics Endopeptidases / genetics Genetic Association Studies / methods Glutamate Decarboxylase / genetics Immobilization Mice Mice, Inbred C57BL / genetics Mice, Inbred Strains / genetics Quantitative Trait Loci / genetics* Sequence Deletion Tail / anatomy & histology Tail / physiology* gamma-Aminobutyric Acid
IF 27.605
Times Cited 61
DNA material MSM Mouse BAC (RDB04214) MSMg01-414M07
Mice RBRC00209 RBRC01852