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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.

    McDearmon EL, Patel KN, Ko CH, Walisser JA, Schook AC, Chong JL, Wilsbacher LD, Song EJ, Hong HK, Bradfield CA, Takahashi JS.

    Source

    Howard 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]

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