Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice.
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.
Pubmed ID: 17124323 RIS Download
ARNTL Transcription Factors | Animals | Basic Helix-Loop-Helix Transcription Factors | Body Weight | Brain | Calcinosis | Cell Cycle Proteins | Chromosomes, Artificial, Bacterial | Circadian Rhythm | Gene Expression | Longevity | Mice | Mice, Inbred C57BL | Mice, Transgenic | Motor Activity | Muscle, Skeletal | Nuclear Proteins | Organ Specificity | Period Circadian Proteins | Suprachiasmatic Nucleus | Tendons | Transcription Factors