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

被引：273

作者：

McDearmon, Erin L.

Patel, Kush N.

Ko, Caroline H.

Walisser, Jacqueline A.

Schook, Andrew C.

Chong, Jason L.

Wilsbacher, Lisa D.

Song, Eun J.

Hong, Hee-Kyung

Bradfield, Christopher A.

Takahashi, Joseph S.

机构：

[1] Northwestern Univ, Dept Neurobiol & Physiol, Howard Hughes Med Inst, Evanston, IL 60208 USA

[2] Univ Toronto, Dept Psychol, Toronto, ON M5S 3G3, Canada

[3] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA

来源：

SCIENCE | 2006年 / 314卷 / 5803期

关键词：

D O I：

10.1126/science.1132430

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

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页码：1304 / 1308

页数：5

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