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Science. 2006 Nov 24;314(5803):1304-8.

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

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  • 1Howard Hughes Medical Institute, Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.

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-/- 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.

PMID:
17124323
[PubMed - indexed for MEDLINE]
PMCID:
PMC3756687
Free PMC Article
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