Publication Date:
2006-11-25
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756687/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756687/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- P50 MH074924/MH/NIMH NIH HHS/ -- R01 ES005703/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2006 Nov 24;314(5803):1304-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17124323" target="_blank"〉PubMed〈/a〉
Keywords:
ARNTL Transcription Factors
;
Animals
;
Basic Helix-Loop-Helix Transcription Factors/genetics/*physiology
;
Body Weight
;
Brain/*metabolism
;
Calcinosis
;
Cell Cycle Proteins/genetics
;
Chromosomes, Artificial, Bacterial
;
*Circadian Rhythm
;
Gene Expression
;
Longevity
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
*Motor Activity
;
Muscle, Skeletal/*metabolism
;
Nuclear Proteins/genetics
;
Organ Specificity
;
Period Circadian Proteins
;
Suprachiasmatic Nucleus/metabolism
;
Tendons/pathology
;
Transcription Factors/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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