Takumi T, Matsubara C, Shigeyoshi Y, Taguchi K, Yagita K, Maebayashi Y, Sakakida Y, Okumura K, Takashima N, Okamura H
Department of Anatomy and Brain Science, Kobe University School of Medicine, Japan.
Genes Cells. 1998 Mar;3(3):167-76. doi: 10.1046/j.1365-2443.1998.00178.x.
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.
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.
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.
最近有报道称，在哺乳动物中发现了两种可能的生物钟基因（Clock、Per1）。特别是mPer1（第一个被鉴定出的小鼠周期基因），在哺乳动物生物钟中心视交叉上核（SCN）中呈现昼夜节律性表达。然而，仅mPer1和Clock作为生物钟组件，可能不足以解释昼夜节律振荡和同步化中的所有事件。
从鼠脑中分离出了一种哺乳动物周期互补DNA，即mPer2。mPer2的氨基酸序列与mPer1和果蝇周期蛋白（dPer）相似，这表明mPer2是包含mPer1（其本身是dPer的同源物）的基因家族的成员。mPer2 mRNA主要在SCN中表达。在SCN中强烈的昼夜节律性表达支持了mPer2是一种生物钟基因的观点。mPer2在持续黑暗条件下的主观下午强烈表达，这与呈早晨相位的生物钟基因mPer1不同。我们精确的定量原位杂交显示，与mPer1相比，在光照-黑暗（LD）条件下mPer2转录本的峰值表达延迟8小时，在黑暗-黑暗（DD）条件下延迟4小时。在主观夜晚早期短暂的光照暴露会促使运动节律发生相位偏移，与mPer1 mRNA诱导相比，会诱导mPer2转录本短暂增加且起始延迟。此外，mPer2与mPer1在单个SCN细胞中共表达。
哺乳动物周期基因表现出分子异质性，每个基因由不同的振荡器组成，可能有助于在哺乳动物振荡细胞中建立稳定的昼夜节律。
