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Article Dans Une Revue PLoS Genetics Année : 2020

High-throughput discovery of genetic determinants of circadian misalignment

Tao Zhang
Pancheng Xie
  • Fonction : Auteur
Yingying Dong
  • Fonction : Auteur
Zhiwei Liu
Fei Zhou
  • Fonction : Auteur
Dejing Pan
  • Fonction : Auteur
Yue Gu
  • Fonction : Auteur
Qingyu Wu
  • Fonction : Auteur
Lauryl Nutter
Colin Mckerlie
Ann Flenniken
Steve Brown
K. Lloyd
Jun Yan
  • Fonction : Auteur
Xiang Gao
Chi-Kuang Leo Wang
  • Fonction : Auteur
Yi Liu
  • Fonction : Auteur
  • PersonId : 4334
  • IdHAL : yi-liu
Ling Yang
  • Fonction : Auteur
Ying Xu
  • Fonction : Auteur

Résumé

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.
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Origine : Publication financée par une institution

Dates et versions

hal-03065538 , version 1 (29-11-2022)

Identifiants

Citer

Tao Zhang, Pancheng Xie, Yingying Dong, Zhiwei Liu, Fei Zhou, et al.. High-throughput discovery of genetic determinants of circadian misalignment. PLoS Genetics, 2020, 16 (1), pp.e1008577. ⟨10.1371/journal.pgen.1008577⟩. ⟨hal-03065538⟩

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