The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period

被引：369

作者：

Godinho, Sofia I. H.

Maywood, Elizabeth S.

Shaw, Linda

Tucci, Valter

Barnard, Alun R.

Busino, Luca

Pagano, Michele

Kendall, Rachel

Quwailid, Mohamed M.

Romero, M. Rosario

O'Neill, John

Chesham, Johanna E.

Brooker, Debra

Lalanne, Zuzanna

Hastings, Michael H.

Nolan, Patrick M. ^{[1
]}

机构：

[1] MRC, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England

[2] MRC, Mol Biol Lab, Div Neurobiol, Cambridge CB2 2QH, England

[3] NYU, Dept Pathol, Inst Canc, Sch Med, New York, NY 10016 USA

来源：

SCIENCE | 2007年 / 316卷 / 5826期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1126/science.1141138

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

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页码：897 / 900

页数：4

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