Mop3 is an essential component of the master circadian pacemaker in mammals

Maureen K. Bunger; Lisa D. Wilsbacher; Susan M. Moran; Cynthia Clendenin; Laurel A. Radcliffe; John B. Hogenesch; M. Celeste Simon; Joseph S. Takahashi; Christopher A. Bradfield

doi:10.1016/S0092-8674(00)00205-1

Mop3 is an essential component of the master circadian pacemaker in mammals

Maureen K. Bunger, Lisa D. Wilsbacher, Susan M. Moran, Cynthia Clendenin, Laurel A. Radcliffe, John B. Hogenesch, M. Celeste Simon, Joseph S. Takahashi, Christopher A. Bradfield

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1271 Scopus citations

Abstract

Circadian oscillations in mammalian physiology and behavior are regulated by an endogenous biological clock. Here we show that loss of the PAS protein MOP3 (also known as BMAL1) in mice results in immediate and complete loss of circadian rhythmicity in constant darkness. Additionally, locomotor activity in light-dark (LD) cycles is impaired and activity levels are reduced in Mop3^-/- mice. Analysis of Period gene expression in the suprachiasmatic nucleus (SCN) indicates that these behavioral phenotypes arise from loss of circadian function at the molecular level. These results provide genetic evidence that MOP3 is the bona fide hetero-dimeric partner of mCLOCK. Furthermore, these data demonstrate that MOP3 is a nonredundant and essential component of the circadian pacemaker in mammals.

Original language	English (US)
Pages (from-to)	1009-1017
Number of pages	9
Journal	Cell
Volume	103
Issue number	7
DOIs	https://doi.org/10.1016/S0092-8674(00)00205-1
State	Published - Dec 22 2000

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(00)00205-1

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title = "Mop3 is an essential component of the master circadian pacemaker in mammals",

abstract = "Circadian oscillations in mammalian physiology and behavior are regulated by an endogenous biological clock. Here we show that loss of the PAS protein MOP3 (also known as BMAL1) in mice results in immediate and complete loss of circadian rhythmicity in constant darkness. Additionally, locomotor activity in light-dark (LD) cycles is impaired and activity levels are reduced in Mop3-/- mice. Analysis of Period gene expression in the suprachiasmatic nucleus (SCN) indicates that these behavioral phenotypes arise from loss of circadian function at the molecular level. These results provide genetic evidence that MOP3 is the bona fide hetero-dimeric partner of mCLOCK. Furthermore, these data demonstrate that MOP3 is a nonredundant and essential component of the circadian pacemaker in mammals.",

author = "Bunger, {Maureen K.} and Wilsbacher, {Lisa D.} and Moran, {Susan M.} and Cynthia Clendenin and Radcliffe, {Laurel A.} and Hogenesch, {John B.} and Simon, {M. Celeste} and Takahashi, {Joseph S.} and Bradfield, {Christopher A.}",

note = "Funding Information: We thank Martha H. Vitaterna for assistance with the ANOVA analyses and Ravi Allada for helpful discussions. This work was supported by The National Institutes of Health Grants P30-CA07175 and ES05703. C. A. Bradfield was supported through a Burroughs Wellcome Scholarship in Toxicology. M. Bunger was supported by a Mary Engsberg Fellowship in Cancer Research. L. D. Wilsbacher is a Fellow in the Medical Scientist Training Program. M. C. Simon and J. S. Takahashi are Investigators in the Howard Hughes Medical Institute.",

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doi = "10.1016/S0092-8674(00)00205-1",

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T1 - Mop3 is an essential component of the master circadian pacemaker in mammals

AU - Bunger, Maureen K.

AU - Wilsbacher, Lisa D.

AU - Moran, Susan M.

AU - Clendenin, Cynthia

AU - Radcliffe, Laurel A.

AU - Hogenesch, John B.

AU - Simon, M. Celeste

AU - Takahashi, Joseph S.

AU - Bradfield, Christopher A.

N1 - Funding Information: We thank Martha H. Vitaterna for assistance with the ANOVA analyses and Ravi Allada for helpful discussions. This work was supported by The National Institutes of Health Grants P30-CA07175 and ES05703. C. A. Bradfield was supported through a Burroughs Wellcome Scholarship in Toxicology. M. Bunger was supported by a Mary Engsberg Fellowship in Cancer Research. L. D. Wilsbacher is a Fellow in the Medical Scientist Training Program. M. C. Simon and J. S. Takahashi are Investigators in the Howard Hughes Medical Institute.

PY - 2000/12/22

Y1 - 2000/12/22

N2 - Circadian oscillations in mammalian physiology and behavior are regulated by an endogenous biological clock. Here we show that loss of the PAS protein MOP3 (also known as BMAL1) in mice results in immediate and complete loss of circadian rhythmicity in constant darkness. Additionally, locomotor activity in light-dark (LD) cycles is impaired and activity levels are reduced in Mop3-/- mice. Analysis of Period gene expression in the suprachiasmatic nucleus (SCN) indicates that these behavioral phenotypes arise from loss of circadian function at the molecular level. These results provide genetic evidence that MOP3 is the bona fide hetero-dimeric partner of mCLOCK. Furthermore, these data demonstrate that MOP3 is a nonredundant and essential component of the circadian pacemaker in mammals.

AB - Circadian oscillations in mammalian physiology and behavior are regulated by an endogenous biological clock. Here we show that loss of the PAS protein MOP3 (also known as BMAL1) in mice results in immediate and complete loss of circadian rhythmicity in constant darkness. Additionally, locomotor activity in light-dark (LD) cycles is impaired and activity levels are reduced in Mop3-/- mice. Analysis of Period gene expression in the suprachiasmatic nucleus (SCN) indicates that these behavioral phenotypes arise from loss of circadian function at the molecular level. These results provide genetic evidence that MOP3 is the bona fide hetero-dimeric partner of mCLOCK. Furthermore, these data demonstrate that MOP3 is a nonredundant and essential component of the circadian pacemaker in mammals.

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Mop3 is an essential component of the master circadian pacemaker in mammals

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