TY - JOUR
T1 - Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice
AU - McDearmon, Erin L.
AU - Patel, Kush N.
AU - Ko, Caroline H.
AU - Walisser, Jacqueline A.
AU - Schook, Andrew C.
AU - Chong, Jason L.
AU - Wilsbacher, Lisa D.
AU - Song, Eun J.
AU - Hong, Hee Kyung
AU - Bradfield, Christopher A.
AU - Takahashi, Joseph S.
PY - 2006/11/24
Y1 - 2006/11/24
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/33751565112
U2 - 10.1126/science.1132430
DO - 10.1126/science.1132430
M3 - Article
C2 - 17124323
AN - SCOPUS:33751565112
SN - 0036-8075
VL - 314
SP - 1304
EP - 1308
JO - Science
JF - Science
IS - 5803
ER -