A clock shock: mouse CLOCK is not required for circadian oscillator function - PubMed

Abstract

The circadian clock mechanism in the mouse is composed of interlocking transcriptional feedback loops. Two transcription factors, CLOCK and BMAL1, are believed to be essential components of the circadian clock. We have used the Cre-LoxP system to generate whole-animal knockouts of CLOCK and evaluated the resultant circadian phenotypes. Surprisingly, CLOCK-deficient mice continue to express robust circadian rhythms in locomotor activity, although they do have altered responses to light. At the molecular and biochemical levels, clock gene mRNA and protein levels in both the master clock in the suprachiasmatic nuclei and a peripheral clock in the liver show alterations in the CLOCK-deficient animals, although the molecular feedback loops continue to function. Our data challenge a central feature of the current mammalian circadian clock model regarding the necessity of CLOCK:BMAL1 heterodimers for clock function.

Comment in

• Keeping time without a clock.

  Collins B, Blau J. Collins B, et al. Neuron. 2006 May 4;50(3):348-50. doi: 10.1016/j.neuron.2006.04.022. Neuron. 2006. PMID: 16675389 Review.

• Rodent rhythmicity studies: Use of unfavorable light regimes.

  Lee Kavanau J. Lee Kavanau J. Med Hypotheses. 2007;68(2):455-6. doi: 10.1016/j.mehy.2006.07.011. Epub 2006 Sep 11. Med Hypotheses. 2007. PMID: 16965860 No abstract available.

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