Genetic and molecular analysis of wild-derived arrhythmic mice

Tsuyoshi Watanabe, Tohru Suzuki, Akira Ishikawa, Yuki Yokota, Hiroki R. Ueda, Rikuhiro G. Yamada, Hajime Tei, Saki Imai, Shigeru Tomida, Junya Kobayashi, Emiko Naito, Shinobu Yasuo, Nobuhiro Nakao, Takao Namikawa, Takashi Yoshimura, Shizufumi Ebihara

Research output: Contribution to journalArticle

Abstract

A new circadian variant was isolated by screening the intercross offspring of wild-caught mice (Mus musculus castaneus). This variant was characterized by an initial maintenance of damped oscillations and subsequent loss of rhythmicity after being transferred from light-dark (LD) cycles, to constant darkness (DD). To map the genes responsible for the persistence of rhythmicity (circadian ratio) and the length of free-running period (τ), quantitative trait locus (QTL) analysis was performed using F2 mice obtained from an F1 cross between the circadian variant and C57BL/6J mice. As a result, a significant QTL with a main effect for circadian ratio (Arrhythmicity; Arrh-1) was mapped on Chromosome (Chr) 8. For τ, four significant QTLs, Short free-running period (Sfp-1) (Chr 1), Sfp-2 (Chr 6), Sfp-3 (Chr 8), Sfp-4 (Chr 11) were determined. An epistatic interaction was detected between Chr 3 (Arrh-2) and Chr 5 (Arrh-3). An in situ hybridization study of clock genes and mouse Period 1::luciferase (mPer1::luc) real-time monitoring analysis in the suprachiasmatic nucleus (SCN) suggested that arrhythmicity in this variant might not be attributed to core circadian mechanisms in the SCN neurons. Our strategy using wild-derived variant mice may provide a novel opportunity to evaluate circadian and its related disorders in human that arise from the interaction between multiple variant genes.

Original languageEnglish
Article numbere4301
JournalPloS one
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 28 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Watanabe, T., Suzuki, T., Ishikawa, A., Yokota, Y., Ueda, H. R., Yamada, R. G., Tei, H., Imai, S., Tomida, S., Kobayashi, J., Naito, E., Yasuo, S., Nakao, N., Namikawa, T., Yoshimura, T., & Ebihara, S. (2009). Genetic and molecular analysis of wild-derived arrhythmic mice. PloS one, 4(1), [e4301]. https://doi.org/10.1371/journal.pone.0004301