PLoS ONE (Jan 2009)

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

DOI
https://doi.org/10.1371/journal.pone.0004301
Journal volume & issue
Vol. 4, no. 1
p. e4301

Abstract

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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 (tau), quantitative trait locus (QTL) analysis was performed using F(2) mice obtained from an F(1) 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 tau, 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 Period1::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.