Mop3 is an essential component of the master circadian pacemaker in mammals.
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 heterodimeric partner of mCLOCK. Furthermore, these data demonstrate that MOP3 is a nonredundant and essential component of the circadian pacemaker in mammals.
Bunger
M K
MK
The McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, WI 53706, USA.
Wilsbacher
L D
LD
Moran
S M
SM
Clendenin
C
C
Radcliffe
L A
LA
Hogenesch
J B
JB
Simon
M C
MC
Takahashi
J S
JS
Bradfield
C A
CA
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001522:Behavior, Animal; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D015342:DNA Probes; D004268:DNA-Binding Proteins; D015870:Gene Expression / Q000502:physiology; D008322:Mammals; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D010641:Phenotype; D013493:Suprachiasmatic Nucleus / Q000737:chemistry / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D014157:Transcription Factors; C538960:BMAL1 protein, human; C486615:BMAL2 protein, human; C538961:Bmal1 protein, mouse; C431792:Arntl2 protein, mouse; C498260:Dbp protein, mouse; C539022:PER1 protein, human; C421902:PER2 protein, human; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse