THE MOUSE CLOCK MUTATION BEHAVES AS AN ANTIMORPH AND MAPS WITHIN THE W-19H DELETION, DISTAL OF KIT

Clock is a semidominant mutation identified from an N-ethyl-N-nitrosou rea mutagenesis screen in mice. Mice carrying the Clock mutation exhib it abnormalities of circadian behavior, including lengthening of endog enous period and loss of rhythmicity. To identify the gene affected by this mutation, we have generated a high-resolution genetic map (> 180 0 meioses) of the Clock locus. We report that Clock is 0.7 cM distal o f Kit on mouse chromosome 5. Mapping shows that Clock lies within the W-19H deletion. Complementation analysis of different Clock and W-19H compound genotypes indicates that the Clock mutation behaves as an ant imorph. This antimorphic behavior of Clock strongly argues that Clock defines a gene centrally involved in the mammalian circadian system.