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 journalArticle

514 Citations (Scopus)

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

Fingerprint

Bacterial Artificial Chromosomes
Circadian Clocks
Chromosomes
Transgenes
Clocks
Genes
Organism Cloning
Helix-Loop-Helix Motifs
Cloning
Base Pairing
Transgenic Mice
Clone Cells
Phenotype
Transcription
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Antoch, Marina P. ; Song, Eun Joo ; Chang, Anne Marie ; Vitaterna, Martha Hotz ; Zhao, Yaliang ; Wilsbacher, Lisa D ; Sangoram, Ashvin M. ; King, David P. ; Pinto, Lawrence H. ; Takahashi, Joseph S. / Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. In: Cell. 1997 ; Vol. 89, No. 4. pp. 655-667.
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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.",
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Antoch, MP, Song, EJ, Chang, AM, Vitaterna, MH, Zhao, Y, Wilsbacher, LD, Sangoram, AM, King, DP, Pinto, LH & Takahashi, JS 1997, 'Functional identification of the mouse circadian Clock gene by transgenic BAC rescue', Cell, vol. 89, no. 4, pp. 655-667. https://doi.org/10.1016/S0092-8674(00)80246-9

Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. / Antoch, Marina P.; Song, Eun Joo; Chang, Anne Marie; Vitaterna, Martha Hotz; Zhao, Yaliang; Wilsbacher, Lisa D; Sangoram, Ashvin M.; King, David P.; Pinto, Lawrence H.; Takahashi, Joseph S.

In: Cell, Vol. 89, No. 4, 16.05.1997, p. 655-667.

Research output: Contribution to journalArticle

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AU - Song, Eun Joo

AU - Chang, Anne Marie

AU - Vitaterna, Martha Hotz

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AU - Wilsbacher, Lisa D

AU - Sangoram, Ashvin M.

AU - King, David P.

AU - Pinto, Lawrence H.

AU - Takahashi, Joseph S.

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