Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock.
Mice carrying a null mutation in the Period 1 (mPer1) gene were generated using embryonic stem cell technology. Homozygous mPer1 mutants display a shorter circadian period with reduced precision and stability. Mice deficient in both mPer1 and mPer2 do not express circadian rhythms. While mPER2 regulates clock gene expression at the transcriptional level, mPER1 is dispensable for the rhythmic RNA expression of mPer1 and mPer2 and may instead regulate mPER2 at a posttranscriptional level. Studies of clock-controlled genes (CCGs) reveal a complex pattern of regulation by mPER1 and mPER2, suggesting independent controls by the two proteins over some output pathways. Genes encoding key enzymes in heme biosynthesis are under circadian control and are regulated by mPER1 and mPER2. Together, our studies show that mPER1 and mPER2 have distinct and complementary roles in the mouse clock mechanism.
Zheng
B
B
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Albrecht
U
U
Kaasik
K
K
Sage
M
M
Lu
W
W
Vaishnav
S
S
Li
Q
Q
Sun
Z S
ZS
Eichele
G
G
Bradley
A
A
Lee
C C
CC
D000818:Animals; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D008029:Lighting; D008322:Mammals; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D056950:Period Circadian Proteins; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; 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