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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

Authors

  • McDearmon EL
  • Patel KN
  • Ko CH
  • Walisser JA
  • Schook AC
  • Chong JL
  • Wilsbacher LD
  • Song EJ
  • Hong HK
  • Bradfield CA
  • Takahashi JS

Journal

Science (New York, N.Y.)

Publication Data

November 24, 2006

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:

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