1. A Clock Shock: Mouse CLOCK Is Not Required for Circadian Oscillator Function
- Author
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Christopher M. Lambert, Elizabeth S. Maywood, Steven M. Reppert, David R. Weaver, Elizabeth Noton, and Jason P. DeBruyne
- Subjects
medicine.medical_specialty ,Light ,Neuroscience(all) ,Period (gene) ,Circadian clock ,CLOCK Proteins ,Mice, Transgenic ,Biology ,Motor Activity ,MOLNEURO ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Biological Clocks ,Internal medicine ,medicine ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,Circadian rhythm ,RNA, Messenger ,Oscillating gene ,030304 developmental biology ,Feedback, Physiological ,Mice, Knockout ,0303 health sciences ,General Neuroscience ,ARNTL Transcription Factors ,Bacterial circadian rhythms ,Cell biology ,Circadian Rhythm ,CLOCK ,Mice, Inbred C57BL ,Endocrinology ,Phenotype ,Light effects on circadian rhythm ,Liver ,Trans-Activators ,Master clock ,Suprachiasmatic Nucleus ,SYSNEURO ,Dimerization ,030217 neurology & neurosurgery ,Photic Stimulation - Abstract
SummaryThe 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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