The After-Hours Mutant Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period
Copyright policy )The After-Hours Mutant Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period
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.
- University of Oxford United Kingdom
- MRC Laboratory of Molecular Biology United Kingdom
- Medical Research Council United Kingdom
- New York University United States
Male, Flavoproteins, F-Box Proteins, ARNTL Transcription Factors, CLOCK Proteins, Cell Cycle Proteins, Circadian Rhythm, Cryptochromes, Mice, Amino Acid Substitution, Gene Expression Regulation, Liver, COS Cells, Chlorocebus aethiops, Basic Helix-Loop-Helix Transcription Factors, Animals, Female, Amino Acid Sequence, Lung, Crosses, Genetic
Male, Flavoproteins, F-Box Proteins, ARNTL Transcription Factors, CLOCK Proteins, Cell Cycle Proteins, Circadian Rhythm, Cryptochromes, Mice, Amino Acid Substitution, Gene Expression Regulation, Liver, COS Cells, Chlorocebus aethiops, Basic Helix-Loop-Helix Transcription Factors, Animals, Female, Amino Acid Sequence, Lung, Crosses, Genetic
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