Publication Date:
2007-04-28
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- MC_U105170643/Medical Research Council/United Kingdom -- MC_U142684172/Medical Research Council/United Kingdom -- MC_U142684173/Medical Research Council/United Kingdom -- MC_U142684175/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 May 11;316(5826):897-900. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463252" target="_blank"〉PubMed〈/a〉
Keywords:
ARNTL Transcription Factors
;
Amino Acid Sequence
;
Amino Acid Substitution
;
Animals
;
Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
;
CLOCK Proteins
;
COS Cells
;
Cell Cycle Proteins/genetics/metabolism
;
Cercopithecus aethiops
;
*Circadian Rhythm/genetics
;
Crosses, Genetic
;
Cryptochromes
;
F-Box Proteins/*genetics/*physiology
;
Female
;
Flavoproteins/genetics/metabolism
;
Gene Expression Regulation
;
Liver/metabolism
;
Lung/metabolism
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C3H
;
Molecular Sequence Data
;
Nuclear Proteins/genetics/metabolism
;
Period Circadian Proteins
;
*Point Mutation
;
Suprachiasmatic Nucleus/metabolism
;
Trans-Activators/genetics/metabolism
;
Transcription Factors/genetics/metabolism
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
