Reduced sleep in Drosophila shaker mutants
Reduced sleep in Drosophila shaker mutants
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DOI：
10.1038/nature03486
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发表时间：
2005-04-28
期刊：
影响因子：
64.8
通讯作者：
Tononi, G
中科院分区：
文献类型：
--
作者：
Cirelli, C;Bushey, D;Tononi, G
我们大多数人每晚睡7-8个小时，如果我们被剥夺了睡眠，我们的表现会受到很大影响；然而，少数人只睡3-4个小时就能做得很好--这似乎是家族遗传的特征。确定哪些基因是这种表型的基础，可以揭示睡眠的机制和功能。为了做到这一点，我们对黑腹果蝇进行了突变，因为果蝇也会睡上几个小时，当睡眠被剥夺时，会表现出睡眠反弹和表现障碍。通过筛选9000个突变株系，我们发现了迷你睡眠(MNS)，这是一种睡眠时间是野生型的三分之一的品系。我们发现，MNS果蝇在许多任务中表现正常，保持了睡眠稳态，但没有受到睡眠剥夺的影响。然后，我们证明了MNS果蝇在Shaker基因的保守区域中携带着一个点突变。此外，在剔除了许多世代积累的遗传修饰因素后，其他Shaker等位基因也变成了短睡者，无法补充MNS的表型。最后，我们发现睡眠时间较短的震颤蝇寿命较短。Shaker编码一种控制膜复极化和递质释放的电压依赖性钾通道，因此可能调节睡眠需要或效率。
Most of us sleep 7-8 h per night, and if we are deprived of sleep our performance suffers greatly; however, a few do well with just 3-4 h of sleep-a trait that seems to run in families. Determining which genes underlie this phenotype could shed light on the mechanisms and functions of sleep. To do so, we performed mutagenesis in Drosophila melanogaster, because flies also sleep for many hours and, when sleep deprived, show sleep rebound and performance impairments. By screening 9,000 mutant lines, we found minisleep (mns), a line that sleeps for one-third of the wild-type amount. We show that mns flies perform normally in a number of tasks, have preserved sleep homeostasis, but are not impaired by sleep deprivation. We then show that mns flies carry a point mutation in a conserved domain of the Shaker gene. Moreover, after crossing out genetic modifiers accumulated over many generations, other Shaker alleles also become short sleepers and fail to complement the mns phenotype. Finally, we show that short-sleeping Shaker flies have a reduced lifespan. Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency.