The mPer2 gene encodes a functional component of the mammalian circadian clock.
Circadian rhythms are driven by endogenous biological clocks that regulate many biochemical, physiological and behavioural processes in a wide range of life forms. In mammals, there is a master circadian clock in the suprachiasmatic nucleus of the anterior hypothalamus. Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified. The mPer genes share a conserved PAS domain (a dimerization domain found in Per, Arnt and Sim) and show a circadian expression pattern in the suprachiasmatic nucleus. To assess the in vivo function of mPer2, we generated and characterized a deletion mutation in the PAS domain of the mouse mPer2 gene. Here we show that mice homozygous for this mutation display a shorter circadian period followed by a loss of circadian rhythmicity in constant darkness. The mutation also diminishes the oscillating expression of both mPer1 and mPer2 in the suprachiasmatic nucleus, indicating that mPer2 may regulate mPer1 in vivo. These data provide evidence that an mPer gene functions in the circadian clock, and define mPer2 as a component of the mammalian circadian oscillator.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
B
B
Zheng
D W
DW
Larkin
U
U
Albrecht
Z S
ZS
Sun
M
M
Sage
G
G
Eichele
C C
CC
Lee
A
A
Bradley
D000818:Animals; D001683:Biological Clocks / Q000235:genetics* / Q000502:physiology; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D003624:Darkness; D004330:Drosophila; D005583:Fourier Analysis; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D056950:Period Circadian Proteins; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014157:Transcription Factors
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539022:PER1 protein, human; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors