TIMELESS mutation alters phase responsiveness and causes advanced sleep phase.
Ontology highlight
ABSTRACT:
SUBMITTER: Kurien P
PROVIDER: S-EPMC6575169 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
TIMELESS mutation alters phase responsiveness and causes advanced sleep phase.
Kurien Philip P Hsu Pei-Ken PK Leon Jacy J Wu David D McMahon Thomas T Shi Guangsen G Xu Ying Y Lipzen Anna A Pennacchio Len A LA Jones Christopher R CR Fu Ying-Hui YH Ptáček Louis J LJ
Proceedings of the National Academy of Sciences of the United States of America 20190528 24
Many components of the circadian molecular clock are conserved from flies to mammals; however, the role of mammalian Timeless remains ambiguous. Here, we report a mutation in the human <i>TIMELESS</i> (h<i>TIM</i>) gene that causes familial advanced sleep phase (FASP). <i>Tim</i> CRISPR mutant mice exhibit FASP with altered photic entrainment but normal circadian period. We demonstrate that the mutation prevents TIM accumulation in the nucleus and has altered affinity for CRY2, leading to destab ...[more]
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