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

First Author  McDearmon EL Year  2006
Journal  Science Volume  314
Issue  5803 Pages  1304-8
PubMed ID  17124323 Mgi Jnum  J:116189
Mgi Id  MGI:3693150 Doi  10.1126/science.1132430
Citation  McDearmon EL, et al. (2006) Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. Science 314(5803):1304-8
abstractText  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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