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High-throughput discovery of genetic determinants of circadian misalignment
T. Zhang, P. Xie, Y. Dong, Z. Liu, F. Zhou, D. Pan, Z. Huang, Q. Zhai, Y. Gu, Q. Wu, N. Tanaka, Y. Obata, A. Bradley, CJ. Lelliott, Sanger Institute Mouse Genetics Project, LMJ. Nutter, C. McKerlie, AM. Flenniken, MF. Champy, T. Sorg, Y. Herault,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
MC_U142684171
Medical Research Council - United Kingdom
MC_U142684172
Medical Research Council - United Kingdom
UM1 HG006370
NHGRI NIH HHS - United States
UM1 OD023221
NIH HHS - United States
NLK
Directory of Open Access Journals
od 2005
Free Medical Journals
od 2005
Public Library of Science (PLoS)
od 2005-07-01
PubMed Central
od 2005
Europe PubMed Central
od 2005
ProQuest Central
od 2005-07-01
Open Access Digital Library
od 2005-07-01
Open Access Digital Library
od 2005-01-01
Open Access Digital Library
od 2005-01-01
Medline Complete (EBSCOhost)
od 2005-07-01
Health & Medicine (ProQuest)
od 2005-07-01
- MeSH
- cirkadiánní rytmus genetika MeSH
- komplexy ubikvitinligas genetika MeSH
- mutace MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- proteiny vázající telomery genetika MeSH
- receptory oxytocinu genetika MeSH
- represorové proteiny genetika MeSH
- serinové endopeptidasy genetika MeSH
- strojové učení MeSH
- transportní systém aminokyselin y+ genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Circadian systems provide a fitness advantage to organisms by allowing them to adapt to daily changes of environmental cues, such as light/dark cycles. The molecular mechanism underlying the circadian clock has been well characterized. However, how internal circadian clocks are entrained with regular daily light/dark cycles remains unclear. By collecting and analyzing indirect calorimetry (IC) data from more than 2000 wild-type mice available from the International Mouse Phenotyping Consortium (IMPC), we show that the onset time and peak phase of activity and food intake rhythms are reliable parameters for screening defects of circadian misalignment. We developed a machine learning algorithm to quantify these two parameters in our misalignment screen (SyncScreener) with existing datasets and used it to screen 750 mutant mouse lines from five IMPC phenotyping centres. Mutants of five genes (Slc7a11, Rhbdl1, Spop, Ctc1 and Oxtr) were found to be associated with altered patterns of activity or food intake. By further studying the Slc7a11tm1a/tm1a mice, we confirmed its advanced activity phase phenotype in response to a simulated jetlag and skeleton photoperiod stimuli. Disruption of Slc7a11 affected the intercellular communication in the suprachiasmatic nucleus, suggesting a defect in synchronization of clock neurons. Our study has established a systematic phenotype analysis approach that can be used to uncover the mechanism of circadian entrainment in mice.
CELPHEDIA PHENOMIN Institut Clinique de la Souris Illkirch France
European Molecular Biology Laboratory European Bioinformatics Institute Hinxton United Kingdom
Medical Research Council Harwell Institute Harwell United Kingdom
National Laboratory Animal Center National Applied Research Laboratories Taipei Taiwan
RIKEN BioResource Center Tsukuba Japan
School of Medicine and Dentistry Queen Mary University of London London United Kingdom
The Centre for Phenogenomics Toronto Canada
The Wellcome Trust Sanger Institute Wellcome Genome Campus Hinxton United Kingdom
Citace poskytuje Crossref.org
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