The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period
The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period
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DOI：
10.1126/science.1141138
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发表时间：
2007-05-11
期刊：
影响因子：
56.9
通讯作者：
Nolan, Patrick M.
中科院分区：
文献类型：
--
作者：
Godinho, Sofia I. H.;Maywood, Elizabeth S.;Nolan, Patrick M.
通过筛选N-乙基-N-亚硝脲致突变动物的车轮活动节律的变化，我们确定了一种小鼠突变，非工作时间(AFH)。这种突变是Fbxl3中的Cys(358)Ser替换，Fbx13是一种富含亮氨酸重复的F-box蛋白，导致纯合子长达27小时的自由奔跑节律。AFH小鼠的昼夜节律转录和翻译振荡减弱。AFH等位基因显著影响PER2的表达，并延缓了PER2：：荧光素酶组织切片中Cry蛋白的降解速度。我们的体内和体外研究揭示了Fbxl3在哺乳动物昼夜节律中的核心作用。
By screening N-ethyl-N-nitrosourea-mutagenized animals for alterations in rhythms of wheel-running activity, we identified a mouse mutation, after hours (Afh). The mutation, a Cys(358)Ser substitution in Fbxl3, an F-box protein with leucine-rich repeats, results in long free-running rhythms of about 27 hours in homozygotes. Circadian transcriptional and translational oscillations are attenuated in Afh mice. The Afh allele significantly affected Per2 expression and delayed the rate of Cry protein degradation in Per2:: Luciferase tissue slices. Our in vivo and in vitro studies reveal a central role for Fbxl3 in mammalian circadian timekeeping.