A clock shock: Mouse CLOCK is not required for circadian oscillator function
A clock shock: Mouse CLOCK is not required for circadian oscillator function
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DOI：
10.1016/j.neuron.2006.03.041
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发表时间：
2006-05-04
期刊：
影响因子：
16.2
通讯作者：
Reppert, Steven M.
中科院分区：
文献类型：
--
作者：
DeBruyne, Jason P.;Noton, Elizabeth;Reppert, Steven M.
小鼠的生物钟机制由互锁的转录反馈环组成。两个转录因子，CLOCK和BMAL 1，被认为是生物钟的重要组成部分。我们已经使用Cre-LoxP系统来产生CLOCK的全动物敲除，并评估所得的昼夜节律表型。令人惊讶的是，CLOCK缺陷小鼠在运动活动中继续表达强大的昼夜节律，尽管它们对光线的反应确实发生了改变。在分子和生化水平，时钟基因的mRNA和蛋白质水平的主时钟在视交叉上核和外周时钟在肝脏中显示改变在时钟缺陷的动物，虽然分子反馈回路继续发挥作用。我们的数据挑战了当前哺乳动物生物钟模型的一个核心特征，即时钟：BMAL 1异二聚体对时钟功能的必要性。
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.