Duper: A Mutation that Shortens Hamster Circadian Period
Duper: A Mutation that Shortens Hamster Circadian Period
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DOI：
10.1177/0748730411411569
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发表时间：
2011-08-01
影响因子：
3.5
通讯作者：
Bittman, Eric L.
中科院分区：
文献类型：
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作者：
Monecke, Stefanie;Brewer, Judy McKinley;Bittman, Eric L.
纯合型tau突变体（tau(ss)，“超短”）出生的三只叙利亚仓鼠表现出极短的自由运动活动时间（tau（DD）约为17.8小时）。近亲繁殖产生了33只“超级超级”鼠，其tau（DD）为18.09 +/- 0.05小时，低于tau（ss）鼠（20.66 +/- 0.07小时，p < 0.001）。为了验证一个基因（Duper）导致tau蛋白（DD）缩短2小时的假设，我们将超级Duper仓鼠与不相关的tau蛋白（ss）动物进行回交。F-1幼鼠的tau（DD）均与tau（ss）仓鼠相似（19.89 +/- 0.15小时），但F-2幼鼠的18- 20小时表型比例为1:1。与此相反，假设为duper杂合的super duper仓鼠与tau（ss）动物杂交的F-1在18- 20小时表型上呈现1:1的比例，并且super duper F-1后代的近亲繁殖均产生具有极短tau(DD)（17.86 +/- 0.5小时）的F-2幼崽。我们通过与野生型动物杂交，在野生型背景上分离到duper突变。限制性消化鉴定出缺乏突变型CK1 epsilon等位基因的短周期F-2幼崽，这些动物的平均tau（DD）为23.11 +/- 0.04小时。DD出生和饲养的duper仓鼠的tau（DD）显著短于14L:10D饲养的仓鼠（21.92±0.12 h, p < 0.0001）。tau（DD）在tau(s)和tau（ss）仓鼠中的缩短是duper纯合子野生型动物的两倍，表明存在上位性相互作用。F-2代的表型分类符合duper基因隐性表达的预期分布（chi(2) = 6.41, p > 0.1）。CK1 epsilon和CK1 δ编码区碱基序列在super duper和tau（ss）仓鼠之间没有差异。超级突变体的生长速度与tau（ss）动物相似，但在特定的断奶后时间点略有但显著降低。我们得出的结论是，duper代表了一种新的突变，可以大幅减少tau(DD)，并对生理和代谢产生重大影响。
Three animals born to homozygous tau mutant (tau(ss), "super short") Syrian hamsters showed extremely short free-running periods of locomotor activity (tau(DD) of approximately 17.8 hours). Inbreeding produced 33 such "super duper" animals, which had a tau(DD) of 18.09 +/- 0.05 hours, which was shorter than that of tau(ss) hamsters (20.66 +/- 0.07 hours, p < 0.001). To test the hypothesis that a gene (Duper) is responsible for a 2-hour shortening of tau(DD), we backcrossed super duper hamsters to unrelated tau(ss) animals. The F-1 pups uniformly had a tau(DD) similar to that of tau(ss) hamsters (19.89 +/- 0.15 hours), but F-2 animals showed a 1: 1 ratio of the 18- to 20-hour phenotypes. In contrast, the F-1 of a cross between super duper hamsters and tau(ss) animals presumed heterozygous for duper showed a 1: 1 ratio of 18-to 20-hour phenotypes, and inbreeding of the super duper F-1 offspring uniformly produced F-2 pups with extremely short tau(DD) (17.86 +/- 0.5 hours). We isolated the duper mutation on a wild-type background through crossing of super duper with wild-type animals. Restriction digests identified short-period F-2 pups that lack the mutant CK1 epsilon allele, and these animals had a mean tau(DD) of 23.11 +/- 0.04 hours. tau(DD) of duper hamsters born and raised in DD was significantly shorter than in hamsters raised in 14L:10D (21.92 +/- 0.12 hours, p < 0.0001). tau(DD) shortened twice as much in tau(s) and tau(ss) hamsters than in wild-type animals that were homozygous for duper, indicating the presence of epistatic interactions. Assortment of phenotypes in the F-2 generation fit the expected distribution for expression of duper as recessive (chi(2) = 6.41, p > 0.1). Neither CK1 epsilon nor CK1 delta coding region base sequences differed between super duper and tau(ss) hamsters. The growth rate of super duper mutants is similar to that of tau(ss) animals but slightly but significantly reduced at particular postweaning time points. We conclude that duper represents a new mutation that substantially reduces tau(DD) and has significant effects on physiology and metabolism.