Functional central rhythmicity and light entrainment, but not liver and muscle rhythmicity, are Clock independent

May 20, 2006American journal of physiology. Regulatory, integrative and comparative physiology

Body clock controls daily rhythms and light response in the brain but not in liver and muscle

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Abstract

Melatonin production in Clock(Delta19) + MEL mutant mice was rhythmic in constant darkness.

The circadian rhythm of melatonin in these mutants can be influenced by brief daily light pulses.
Rhythmic expression of per2 and prokineticin2 mRNA was observed in the SCN of Clock(Delta19) + MEL mice under normal conditions.
Expression of Clock-related genes Bmal1 and npas2 remained unchanged, while per1 expression was found to be arrhythmic.
In contrast to the SCN, liver and skeletal muscle showed arrhythmic expression of per1, per2, and Bmal1 in the same mutants.
The study indicates that the Clock(Delta19) mutation does not eliminate central rhythmicity or light responsiveness but suggests a potential functional equivalent in the SCN.

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The circadian rhythmicity of hormone secretion, body temperature, and sleep/wakefulness results from an endogenous rhythm of neural activity generated by clock genes in the suprachiasmatic nucleus (SCN). One of these genes, Clock, has been considered essential for the generation of cellular rhythmicity centrally and in the periphery; however, melatonin-proficient Clock(Delta19) + MEL mutant mice retain melatonin rhythmicity, suggesting that their central rhythmicity is intact. Here we show that melatonin production in these mutants was rhythmic in constant darkness and could be entrained by brief single daily light pulses. Under normal light-dark conditions, per2 and prokineticin2 (PK2) mRNA expression was rhythmic in the SCN of Clock(Delta19) + MEL mice. Expression of Bmal1 and npas2 was not altered, whereas per1 expression was arrhythmic. In contrast to the SCN, per1 and per2 expression, as well as Bmal1 expression in liver and skeletal muscle, together with plasma corticosterone, was arrhythmic in Clock(Delta19) + MEL mutant mice in normal light-dark conditions. npas2 mRNA was also arrhythmic in liver but rhythmic in muscle. The Clock(Delta19) mutation does not abolish central rhythmicity and light entrainment, suggesting that a functional Clock homolog, possibly npas2, exists in the SCN. Nevertheless, the SCN of Clock(Delta19) + MEL mutant mice cannot maintain liver and muscle rhythmicity through rhythmic outputs, including melatonin secretion, in the absence of functional Clock expression in the tissues. Therefore, liver and muscle, but not SCN, have an absolute requirement for CLOCK, with as yet unknown Clock-independent factors able to generate the latter.

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Functional central rhythmicity and light entrainment, but not liver and muscle rhythmicity, are Clock independent

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