King D P, Vitaterna M H, Chang A M, Dove W F, Pinto L H, Turek F W, Takahashi J S
National Science Foundation Center for Biological Timing, Northwestern University, Evanston, Illinois 60208-3520, USA.
Genetics. 1997 Jul;146(3):1049-60. doi: 10.1093/genetics/146.3.1049.
Clock is a semidominant mutation identified from an N-ethyl-N-nitrosourea mutagenesis screen in mice. Mice carrying the Clock mutation exhibit abnormalities of circadian behavior, including lengthening of endogenous period and loss of rhythmicity. To identify the gene affected by this mutation, we have generated a high-resolution genetic map (> 1800 meioses) of the Clock locus. We report that Clock is 0.7 cM distal of Kit on mouse chromosome 5. Mapping shows that Clock lies within the W19H deletion. Complementation analysis of different Clock and W19H compound genotypes indicates that the Clock mutation behaves as an antimorph. This antimorphic behavior of Clock strongly argues that Clock defines a gene centrally involved in the mammalian circadian system.
Clock是从小鼠N-乙基-N-亚硝基脲诱变筛选中鉴定出的一种半显性突变。携带Clock突变的小鼠表现出昼夜节律行为异常,包括内源性周期延长和节律性丧失。为了鉴定受该突变影响的基因,我们构建了Clock基因座的高分辨率遗传图谱(>1800个减数分裂)。我们报告Clock位于小鼠5号染色体上Kit基因的远端0.7 cM处。定位显示Clock位于W19H缺失区域内。对不同Clock和W19H复合基因型的互补分析表明,Clock突变表现为反效等位基因。Clock的这种反效等位基因行为有力地表明,Clock定义了一个在哺乳动物昼夜节律系统中起核心作用的基因。