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. |