Molecular analysis of the mammalian circulation rhythm

从小鼠脑中分离到一种新的哺乳动物时期互补DNA--mPer2。MPer2的氨基酸序列与mPer1和果蝇时期(DPer)相似，编码Pas结构域(Pas，存在于Per、ArnT、SIM中的二聚化结构域)，表明mPer2是与dPer同源的mPer1家族。MPer2基因主要在哺乳动物的生物钟中枢视交叉上核(SCN)表达。在恒定的黑暗中，SCN中强健的昼夜节律表达支持mPer2成为有节奏的起搏器。在恒定黑暗条件下，mPer2基因的表达高峰在夜间，而在明暗条件下，mPer2基因的表达高峰在夜间，表明mPer2基因的表达模式不同于日期型时钟mPer1。与mPer1、mPer2和果蝇时期一样，mPer3具有二聚化结构域(PAS)和细胞质定位结构域(O…更多ID)。MPer3转录本在视交叉上核(SCN)表现出明显的昼夜节律。在生物钟的任何阶段，mPer3的表达都不受光照的诱导，这使得该基因有别于mPer1和mPer2。在终板血管层(OVLT)的SCN外也发现了mPer3的循环表达，OVLT是调节节律性促性腺激素产生的一个潜在的关键区域，也是热原诱导的发热现象。因此，mPer3可能有助于SCN内外的起搏功能。为了了解光如何影响哺乳动物的生物钟，我们研究了光对mPer1的影响，mPer1是果蝇Per的同源序列，在SCN中表现出强劲的节律表达。MPer1被短时间暴露于足以重置时钟的光中而迅速被诱导，剂量反应曲线表明mPer1诱导既表现出互易性，又与显性节律的相移有很强的相关性。因此，无论是在暗表达的阶段，还是在对光的反应中，mPer1都与脉孢菌钟基因FRQ相似。在SCN内，mPer1的诱导现象似乎被定位，这表明两种类型的时钟(光响应和光不响应)定位于这个昼夜节律中心。较少

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 … More 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