Molecular analysis of the mammalian circulation rhythm

哺乳动物循环节律的分子分析

• 批准号: 09480212
• 负责人: OKAMURA Hitoshi
• 金额: $ 8.26万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09480212/
• 关键词: clock genes; circadian rhythms; mPer1; mPer2; mPer3; mTim; suprachiasmatic nucleus; mammals; 哺乳類period遺伝子; 内因性リズム; 光誘導

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

从小鼠大脑中分离出一种新的哺乳动物时期互补 DNA mPer2，其编码 PAS 结构域（PAS，存在于 PER、ARNT、SIM 中的二聚化结构域），与 mPer1 和果蝇时期相似。 dPer)，表明 mPer2 与 dPer 的同源物 mPer1 是一个家族。 mPer2 mRNA 主要在生物中心的视交叉上核 (SCN) 中表达。在持续黑暗条件下，SCN 中的强昼夜节律表达支持 mPer2 是一种节律性起搏器，其表达高峰出现在持续黑暗条件下的晚上和明暗条件下的熄灯时间，表明该表达模式。 mPer2 mRNA 与日型时钟 mPer1 不同。哺乳动物周期基因家族的新成员 mPer3 被分离出来，其在小鼠大脑中的表达模式与 mPer1、mPer2 和果蝇相似。 mPer3 具有二聚化结构域 (PAS) 和细胞质定位结构域 (O … 更多 LD)，mPer3 转录物在视交叉上核 (SCN) 中显示出清晰的昼夜节律，mPer3 的表达在任何阶段都不会被暴露于光诱导。 mPer3 的循环表达也被发现在 SCN 外的血管器层中。终末肌 (OVLT) 是调节节律性促性腺激素产生和热原引起的发热现象的潜在关键区域，因此，mPer3 可能有助于 SCN 内部和外部的起搏器功能。为了了解光如何影响哺乳动物的生物钟，我们研究了 mPer3。光对 mPer1 的影响，mPer1 是果蝇 per 的序列同源物，在 SCN 中表现出强烈的节律性表达，短时间暴露于足够水平的光下会迅速诱导 mPer1。重置时钟，剂量反应曲线表明，mPer1 诱导显示出互易性，并且与明显节律的相移具有很强的相关性，因此在暗表达的定相和对光的响应方面，mPer1 与脉孢菌时钟基因 frq 相似。在 SCN 内，mPer1 的感应现象似乎存在局部化，表明在该昼夜节律中存在两种类型的时钟（光响应性和光无响应性）中心.较少

项目成果

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Takumi T, Taguchi K, Miyake S, Sakakida Y, Takashima N, Matsubara C, Maebayashi Y, Okumura K, Takekida S, Yamamoto S, Yagita K, Yan L, Young ML, Okamura, H: "A light independent oscillatory gene mPer3 in mouse SCN and OVLT"EMBO J.. 17. 4753-4759 (1998)

Takumi T、Taguchi K、Miyake S、Sakakida Y、Takashima N、Matsubara C、Maebayashi Y、Okumura K、Takekida S、Yamamoto S、Yagita K、Yan L、Young ML、Okamura、H：“光独立振荡基因 mPer3

Takumi T.: "A light independent oscillatory gene mPer3 in mouse SCN and OVLT."EMBO J.. 17巻. 4753-4759 (1998)

Takumi T.：“小鼠 SCN 和 OVLT 中的光独立振荡基因 mPer3。”EMBO J.. 17. 4753-4759 (1998)

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Tei H.: "Circadian oscillation of a mammalian homologue of the Drosophila period gene."Nature. 389巻. 512-516 (1997)

Tei H.：“果蝇周期基因的哺乳动物同源物的昼夜节律振荡”，《自然》，第 389 卷，第 512-516 卷（1997 年）。