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

Erin L. McDearmon, Kush N. Patel, Caroline H. Ko, Jacqueline A. Walisser, Andrew C. Schook, Jason L. Chong, Lisa D Wilsbacher, Eun J. Song, Hee-kyung Hong, Christopher A. Bradfield, Joseph S. Takahashi*

*Corresponding author for this work

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

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-l- 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.

Original languageEnglish (US)
Pages (from-to)1304-1308
Number of pages5
JournalScience
Volume314
Issue number5803
DOIs
StatePublished - Nov 24 2006

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ARNTL Transcription Factors
Body Weight
Muscles
Brain
Periodicity
Circadian Rhythm
Running
Tendons
Transgenic Mice
Transcription Factors
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

McDearmon, E. L., Patel, K. N., Ko, C. H., Walisser, J. A., Schook, A. C., Chong, J. L., ... Takahashi, J. S. (2006). Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. Science, 314(5803), 1304-1308. https://doi.org/10.1126/science.1132430
McDearmon, Erin L. ; Patel, Kush N. ; Ko, Caroline H. ; Walisser, Jacqueline A. ; Schook, Andrew C. ; Chong, Jason L. ; Wilsbacher, Lisa D ; Song, Eun J. ; Hong, Hee-kyung ; Bradfield, Christopher A. ; Takahashi, Joseph S. / Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. In: Science. 2006 ; Vol. 314, No. 5803. pp. 1304-1308.
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abstract = "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-l- 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.",
author = "McDearmon, {Erin L.} and Patel, {Kush N.} and Ko, {Caroline H.} and Walisser, {Jacqueline A.} and Schook, {Andrew C.} and Chong, {Jason L.} and Wilsbacher, {Lisa D} and Song, {Eun J.} and Hee-kyung Hong and Bradfield, {Christopher A.} and Takahashi, {Joseph S.}",
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McDearmon, EL, Patel, KN, Ko, CH, Walisser, JA, Schook, AC, Chong, JL, Wilsbacher, LD, Song, EJ, Hong, H, Bradfield, CA & Takahashi, JS 2006, 'Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice', Science, vol. 314, no. 5803, pp. 1304-1308. https://doi.org/10.1126/science.1132430

Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. / McDearmon, Erin L.; Patel, Kush N.; Ko, Caroline H.; Walisser, Jacqueline A.; Schook, Andrew C.; Chong, Jason L.; Wilsbacher, Lisa D; Song, Eun J.; Hong, Hee-kyung; Bradfield, Christopher A.; Takahashi, Joseph S.

In: Science, Vol. 314, No. 5803, 24.11.2006, p. 1304-1308.

Research output: Contribution to journalArticle

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AU - Wilsbacher, Lisa D

AU - Song, Eun J.

AU - Hong, Hee-kyung

AU - Bradfield, Christopher A.

AU - Takahashi, Joseph S.

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McDearmon EL, Patel KN, Ko CH, Walisser JA, Schook AC, Chong JL et al. Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. Science. 2006 Nov 24;314(5803):1304-1308. https://doi.org/10.1126/science.1132430