Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1126/science.1141138

Type

Journal article

Journal

Science

Publication Date

11/05/2007

Volume

316

Pages

897 - 900

Keywords

ARNTL Transcription Factors, Amino Acid Sequence, Amino Acid Substitution, Animals, Basic Helix-Loop-Helix Transcription Factors, CLOCK Proteins, COS Cells, Cell Cycle Proteins, Cercopithecus aethiops, Circadian Rhythm, Crosses, Genetic, Cryptochromes, F-Box Proteins, Female, Flavoproteins, Gene Expression Regulation, Liver, Lung, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Molecular Sequence Data, Nuclear Proteins, Period Circadian Proteins, Point Mutation, Suprachiasmatic Nucleus, Trans-Activators, Transcription Factors, Transcription, Genetic