Wager-Smith K, Kay S A
Department of Cell Biology, The Scripps Research Institute, La Jolla, California, USA.
Nat Genet. 2000 Sep;26(1):23-7. doi: 10.1038/79134.
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 entreé 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.
通过在果蝇和小鼠中进行表型驱动的诱变筛选，已成功实现了对行为昼夜节律调节的基因剖析。对这些进化上保守的蛋白质进行克隆和生化分析，已使我们对生物钟机制有了详细的分子层面的认识。很少有行为能像昼夜节律那样，在基因、细胞和解剖学层面得到如此深入的理解。昼夜节律钟如此急切地泄露了她的秘密，以至于我们可能很快就会知晓从基因到行为的完整事件链。运用这种不同寻常的知识程度来攻克遗传学中最具挑战性的问题之一：复杂人类行为障碍的基础，可能会卓有成效。我们在此回顾那些为深入了解昼夜节律钟核心提供途径的基因筛选、由此产生的生物钟机制模型，以及在人类昼夜节律失调研究中使用同源物作为候选基因的前景。
