A clock shock: mouse CLOCK is not required for circadian oscillator function
Department of Neurobiology
Medical Subject Headings
ARNTL Transcription Factors; Animals; Basic Helix-Loop-Helix Transcription Factors; Biological Clocks; CLOCK Proteins; Circadian Rhythm; Dimerization; Feedback, Physiological; Light; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Motor Activity; Phenotype; Photic Stimulation; RNA, Messenger; Suprachiasmatic Nucleus; Trans-Activators
Neuroscience and Neurobiology
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.
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Citation: Neuron. 2006 May 4;50(3):465-77. Link to article on publisher's site