Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests

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, Shizufumi Ebihara

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66 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)688-695
Number of pages8
JournalNature Genetics
Volume41
Issue number6
DOIs
Publication statusPublished - 01-06-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics

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    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. (2009). Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests. Nature Genetics, 41(6), 688-695. https://doi.org/10.1038/ng.344