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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

526 Scopus citations

Abstract

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
JournalCell
Volume89
Issue number4
DOIs
StatePublished - May 16 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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