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

Science (New York, N.Y.) | Nov 24, 2006

http://www.ncbi.nlm.nih.gov/pubmed/17124323

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

Mesh terms: 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

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Associated grants

  • Agency: NIMH NIH HHS, Id: P50 MH074924
  • Agency: NIMH NIH HHS, Id: P50 MH074924
  • Agency: NIEHS NIH HHS, Id: R01 ES005703
  • Agency: NIEHS NIH HHS, Id: R01 ES005703
  • Agency: Howard Hughes Medical Institute, Id:

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