A novel Bmal1 mutant mouse reveals essential roles of the C-terminal domain on circadian rhythms

Noheon Park, Hee Dae Kim, Solmi Cheon, Hansang Row, Jiyeon Lee, Dong Hee Han, Sehyung Cho, Kyungjin Kim

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Article numbere0138661
JournalPloS one
Issue number9
StatePublished - Sep 22 2015

ASJC Scopus subject areas

  • General


Dive into the research topics of 'A novel Bmal1 mutant mouse reveals essential roles of the C-terminal domain on circadian rhythms'. Together they form a unique fingerprint.

Cite this