BACKGROUND: In mammals, two possible clock genes (Clock, Per1) have very recently been reported. mPer1 (the first identified mouse period gene), in particular, shows a circadian expression in suprachiasmatic nuclei (SCN), the mammalian circadian centre. However, only mPer1 and Clock as clock components may not be sufficient to understand all the events in circadian oscillation and entrainment. RESULTS: A mammalian period complementary DNA, mPer2, has been isolated from the mouse brain. The amino acid sequence of mPer2 is similar to mPer1 and Drosophila Period (dPer), indicating that mPer2 is a member of the family which contains mPer1, itself a homologue of dPer. mPer2 mRNA is predominantly expressed in SCN. A robust circadian rhythmic expression in the SCN supports the view that mPer2 is a clock gene. mPer2 is strongly expressed at the subjective afternoon in constant darkness, distinct from a morning-phase clock mPer1. Our precise quantitative in situ hybridizations have revealed that the peak expression of mPer2 transcripts is delayed by 8 h in LD (light-dark) or 4 h in DD (dark-dark) conditions when compared to mPer1. A short brief light exposure at the early subjective night, prompting a phase-shift in locomotor rhythms, induces a transient increase of mPer2 transcripts with delayed onset, as compared to mPer1 mRNA induction. Furthermore, mPer2 is co-expressed with mPer1 in single SCN cells. CONCLUSIONS: Mammalian period genes show molecular heterogeneity, each of which is composed of a different oscillator, and may serve to establish stable circadian rhythms in mammalian oscillating cells.

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