Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock

被引:742
作者
Zheng, BH
Albrecht, U
Kaasik, K
Sage, M
Lu, WQ
Vaishnav, S
Li, Q
Sun, ZS
Eichele, G
Bradley, A
Lee, CC
机构
[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[2] Baylor Coll Med, Verna & Marrs Mclean Dept Biochem, Houston, TX 77030 USA
[3] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0092-8674(01)00380-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:683 / 694
页数:12
相关论文
共 53 条
  • [51] The tick-tock of the biological clock
    Young, MW
    [J]. SCIENTIFIC AMERICAN, 2000, 282 (03) : 64 - 71
  • [52] The mPer2 gene encodes a functional component of the mammalian circadian clock
    Zheng, BH
    Larkin, DW
    Albrecht, U
    Sun, ZS
    Sage, M
    Eichele, G
    Lee, CC
    Bradley, A
    [J]. NATURE, 1999, 400 (6740) : 169 - 173
  • [53] Three period homologs in mammals:: Differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain
    Zylka, MJ
    Shearman, LP
    Weaver, DR
    Reppert, SM
    [J]. NEURON, 1998, 20 (06) : 1103 - 1110