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 professes in a wide range o f life forms'. In mammals, there is a master circadian clock in the suprach iasmatic nucleus of the anterior hypothalamus. Three putative mammalian hom ologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene per iod (per) have been identified(2-8). The mPer genes share a conserved PAS d omain (a dimerization domain found in Per, Amt and Sim) and show a circadia n expression pattern in the suprachiasmatic nucleus. To assess the in vivo function of mPer2, we generated and characterized a deletion mutation in th e 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 cir cadian rhythmicity in constant darkness. The mutation also diminishes the o scillating expression of both mPer1 and mPer2 in the suprachiasmatic nucleu s, indicating that mPer2 may regulate mPer1 in vivo. These data provide evi dence that an mPer gene functions in the circadian clock, and define mPer2 as a component of the mammalian circadian oscillator.