Circadian expression of clock genes during ontogeny in the rat heart.

Recent studies have suggested that peripheral tissues in mammals have an autonomous circadian oscillator driven by negative feedback loops consisting of periodical expression of clock genes. In the present study we investigated the mechanism that regulates circadian rhythms in mammalian peripheral tissues, and observed developmental aspects in circadian expression of clock genes in the heart of postnatal rats. Daily expression patterns of clock genes (rPer1, rPer2 and BMAL1) and a clock-controlled gene Dbp were examined by Northern blot analysis. Circadian expression of rPer1, BMAL1 and Dbp mRNAs started between postnatal day 2 (P2) and P5, but rPer2 mRNA did not show rhythmicity until P14. Rhythmic expression of other genes in the heart occurred even in the absence of rhythmic rPer2 expression. These findings suggest that in the rat heart, rhythmic expression of rPer2 was not essential to generate circadian rhythmicity at the early postnatal stage. Judging from mRNA rhythms in the heart, it was probably after P20 that rats established the mature circadian system controlling peripheral rhythms.