Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice

Erin L. McDearmon, Kush N. Patel, Caroline H. Ko, Jacqueline A. Walisser, Andrew C. Schook, Jason L. Chong, Lisa D. Wilsbacher, Eun J. Song, Hee Kyung Hong, Christopher A. Bradfield, Joseph S. Takahashi*

*Corresponding author for this work

Research output: Contribution to journalArticle

198 Scopus citations

Abstract

The basic helix-loop-helix (bHLH)-Per-Arnt-Sim (PAS) domain transcription factor BMAL1 is an essential component of the mammalian circadian pacemaker. Bmal1-/- mice lose circadian rhythmicity but also display tendon calcification and decreased activity, body weight, and longevity. To investigate whether these diverse functions of BMAL1 are tissue-specific, we produced transgenic mice that constitutively express Bmal1 in brain or muscle and examined the effects of rescued gene expression in Bmal1-l- mice. Circadian rhythms of wheel-running activity were restored in brain-rescued Bmal1-/- mice in a conditional manner; however, activity levels and body weight were lower than those of wild-type mice. In contrast, muscle-rescued Bmal1-/- mice exhibited normal activity levels and body weight yet remained behaviorally arrhythmic. Thus, Bmal1 has distinct tissue-specific functions that regulate integrative physiology.

Original languageEnglish (US)
Pages (from-to)1304-1308
Number of pages5
JournalScience
Volume314
Issue number5803
DOIs
StatePublished - Nov 24 2006

ASJC Scopus subject areas

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    McDearmon, E. L., Patel, K. N., Ko, C. H., Walisser, J. A., Schook, A. C., Chong, J. L., Wilsbacher, L. D., Song, E. J., Hong, H. K., Bradfield, C. A., & Takahashi, J. S. (2006). Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. Science, 314(5803), 1304-1308. https://doi.org/10.1126/science.1132430