Circadian rhythm genetics: from flies to mice to humans
Circadian rhythm genetics: from flies to mice to humans
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DOI：
10.1038/79134
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发表时间：
2000-09-01
期刊：
影响因子：
30.8
通讯作者：
Kay, SA
中科院分区：
文献类型：
--
作者：
Wager-Smith, K;Kay, SA
通过在果蝇和小鼠中进行表型驱动的诱变筛选，已经成功地对行为的昼夜节律调节进行了基因剖析。对这些进化上保守的蛋白质进行克隆和生化分析，使得人们对生物钟机制有了详细的分子层面的了解。很少有行为能像昼夜节律这样在基因、细胞和解剖学层面被如此深入地理解。生物钟如此急切地泄露了它的秘密，以至于我们可能很快就会了解从基因到行为的完整事件链。利用这种罕见的知识程度来攻克遗传学中最具挑战性的问题之一——复杂的人类行为障碍的基础，可能会富有成效。我们在此回顾那些为进入生物钟核心提供了途径的基因筛选、由此产生的生物钟机制模型，以及在人类昼夜节律失常研究中使用同源基因作为候选基因的前景。
A successful genetic dissection of the circadian regulation of behaviour has been achieved through phenotype-driven mutagenesis screens in flies and mice. Cloning and biochemical analysis of these evolutionarily conserved proteins has led to detailed molecular insight into the clock mechanism. Few behaviours enjoy the degree of understanding that exists for circadian rhythms at the genetic, cellular and anatomical levels. The circadian clock has so eagerly spilled her secrets that we may soon know the unbroken chain of events from gene to behaviour. It will likely be fruitful to wield this uncommon degree of knowledge to attack one of the most challenging problems in genetics: the basis of complex human behavioural disorders. We review here the genetic screens that provided the entree into the heart of the circadian clock, the model of the clock mechanism that has resulted, and the prospects for using the homologues as candidate genes in studies of human circadian dysrhythmias.