Functional identification of the mouse circadian Clock gene by transgenic BAC rescue

Marina P. Antoch, Eun Joo Song, Anne Marie Chang, Martha Hotz Vitaterna, Yaliang Zhao, Lisa D. Wilsbacher, Ashvin M. Sangoram, David P. King, Lawrence H. Pinto, Joseph S. Takahashi

Research output: Contribution to journalArticlepeer-review

552 Citations (SciVal)


As a complementary approach to positional cloning, we used in vivo complementation with bacterial artificial chromosome (BAC) clones expressed in transgenic mice to identify the circadian Clock gene. A 140 kb BAC transgene completely rescued both the long period and the loss-of-rhythm phenotypes in Clock mutant mice. Analysis with overlapping BAC transgenes demonstrates that a large transcription unit spanning ~100,000 base pairs is the Clock gene and encodes a novel basic-helix-loop-helix-PAS domain protein. Overexpression of the Clock transgene can shorten period length beyond the wild-type range, which provides additional evidence that Clock is an integral component of the circadian pacemaking system. Taken together, these results provide a proof of principle that 'cloning by rescue' is an efficient and definifive method in mice.

Original languageEnglish (US)
Pages (from-to)655-667
Number of pages13
Issue number4
StatePublished - May 16 1997

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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