Cited time in webofscience Cited time in scopus

A Novel Bmal1 Mutant Mouse Reveals Essential Roles of the C-Terminal Domain on Circadian Rhythms

A Novel Bmal1 Mutant Mouse Reveals Essential Roles of the C-Terminal Domain on Circadian Rhythms
Park, NoheonKim, Hee-DaeCheon, SolmiRow, HansangLee, JiyeonHan, Dong-HeeCho, SehyungKim, Kyung Jin
DGIST Authors
Kim, Kyung Jin
Issued Date
Article Type
Animal CellAnimal ExperimentAnimal TissueBMAL1 GeneCarboxy Terminal SequenceCircadian RhythmControlled StudyDarknessDimerizationEmbryoEmbryonic Stem CellFemaleFibroblast CultureGene ExpressionHeterozygoteHomozygoteLiverMaleMessenger RNAMolecular ClockMouseMutantNon-HumanPER1 GenePER1 ProteinPromoter RegionProtein DegradationProtein DomainProtein ExpressionProtein LocalizationReporter GeneSuprachiasmatic NucleusTranscription Factor ARNTLTranscription Factor ClockTranscription Initiation
The mammalian circadian clock is an endogenous biological timer comprised of transcriptional/ translational feedback loops of clock genes. Bmal1 encodes an indispensable transcription factor for the generation of circadian rhythms. Here, we report a new circadian mutant mouse from gene-trapped embryonic stem cells harboring a C-terminus truncated Bmal1 (Bmal1GTΔC) allele. The homozygous mutant (Bmal1GTΔC/GTΔC) mice immediately lost circadian behavioral rhythms under constant darkness. The heterozygous (Bmal1+/ GTΔC) mice displayed a gradual loss of rhythms, in contrast to Bmal1+/- mice where rhythms were sustained. Bmal1GTΔC/GTΔC mice also showed arrhythmic mRNA and protein expression in the SCN and liver. Lack of circadian reporter oscillation was also observed in cultured fibroblast cells, indicating that the arrhythmicity of Bmal1GTΔC/GTΔC mice resulted from impaired molecular clock machinery. Expression of clock genes exhibited distinct responses to the mutant allele in Bmal1+/GTΔC and Bmal1GTΔC/GTΔC mice. Despite normal cellular localization and heterodimerization with CLOCK, overexpressed BMAL1GTΔC was unable to activate transcription of Per1 promoter and BMAL1-dependent CLOCK degradation. These results indicate that the C-terminal region of Bmal1 has pivotal roles in the regulation of circadian rhythms and the Bmal1GTΔC mice constitute a novel model system to evaluate circadian functional mechanism of BMAL1. © 2015 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Public Library of Science
Files in This Item:


기타 데이터 / 3.5 MB / Adobe PDF download
Appears in Collections:
Department of Brain Sciences Brain and BioClock Laboratory 1. Journal Articles


  • twitter
  • facebook
  • mendeley

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.