YAMAGUCHI Shun Kobe University, Department of Anatomy and Brain Science, Assistant Professor, 医学部, 助手 (70304087)
SHIGEYOSHI Yadufumi Kobe Univ., Department of Anatomy and Brain Science, Associate Professor, 医学部, 講師 (20275192)
TAKUMI Toru Kobe University, Department of Anatomy and Brain Science, Associate Professor, 医学部, 講師 (00222092)
|Budget Amount *help
¥12,900,000 (Direct Cost : ¥12,900,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1997 : ¥10,900,000 (Direct Cost : ¥10,900,000)
A new mammalian period complementary DNA, mPer2, has been isolated from mouse brain. The amino acid sequence of mPer2, encoding PAS-domain (PAS, a dimerization domain present in PER, ARNT, SIM), is similar to mPer1 and Drosophila Period (dPer), indicating that mPer2 is a family with mPer1, a homologue of dPer. The mPer2 mRNA is predominantly expressed in the suprachiasmatic nucleus (SCN), the center of biological clocks in mammals. A robust circadian rhythmic expression in the SCN in constant darkness supports mPer2 to be a rhythmic pacemaker. The peak of its expression is at evening in constant dark condition and light-off time in light-dark condition, indicating that expression pattern of mPer2 mRNA is different from day-type clock mPer1.
A new member of the mammalian period gene family, mPer3, was isolated and its expression pattern characterized in the mouse brain. Like mPer1, mPer2 and Drosophila Period, mPer3 has a dimerization domain (PAS) and a cytoplasmic localization domain (O
LD). mPer3 transcripts showed a clear circadian rhythm in the suprachiasmatic nucleus (SCN). Expression of mPer3 was not induced by exposure to light at any phase of the clock, distinguishing this gene from mPer1 and mPer2. Cycling expression of mPer3 was also found outside the SCN in the organum vasculosum lamina terminalis (OVLT), a potentially key region regulating rhythmic gonadotropin production and a pyrogen-induced febrile phenomena. Thus, mPer3 may contribute to pacemaker functions both inside and outside the SCN.
To underst how light might entrain a mammalian circadian clock, we examined the effects of light on mPer1, a sequence homolog of Drosophila per, that exhibits robust rhythmic expression in the SCN. mPer1 is rapidly induced by short duration exposure to light at levels sufficient to reset the clock, and dose response curves reveal that mPer1 induction shows both reciprocity and a strong correlation with phase shifting of the overt rhythm. Thus in both the phasing of dark expression and the response to light mPer1 is similar to Neurospora clock gene frq. Within the SCN there appears to be localization of the induction phenomenon of mPer1, suggesting two types of clocks (light-responsive and light-unresponsive) being localized in this circadian center. Less