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

从小鼠脑中分离到一个新的哺乳动物时期互补DNA mPer2。mPer2编码PAS结构域（PAS，PER，ARNT，SIM中的二聚化结构域），其氨基酸序列与mPer1和果蝇周期（dPer）相似，表明mPer2与dPer的同源物mPer1是一个家族。mPer2 mRNA主要在视交叉上核（SCN）中表达，视交叉上核是哺乳动物的生物钟中心。在持续黑暗中SCN中的强昼夜节律表达支持mPer2是节律性起搏器。在恒定黑暗条件下，mPer2 mRNA的表达高峰出现在晚上，而在光暗条件下，其表达高峰出现在熄灯时间，表明mPer2 mRNA的表达模式与昼型生物钟mPer1不同。与mPer1、mPer2和果蝇Period一样，mPer3具有二聚化结构域（PAS）和胞质定位结构域（O ...更多信息 LD）。mPer3转录本在视交叉上核（SCN）中显示出明显的昼夜节律。mPer3的表达不诱导暴露于光在时钟的任何阶段，区分此基因从mPer1和mPer2。在终板血管器（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和热原诱导发热现象的潜在关键区域。因此，mPer3可能有助于内部和外部的SCN起搏器的功能。为了了解光如何可能夹带哺乳动物的昼夜节律钟，我们研究了光对mPer1的影响，mPer1是果蝇per的序列同源物，在SCN中表现出强大的节奏表达。mPer1是迅速诱导短时间暴露于光的水平足以重置时钟，剂量反应曲线显示，mPer1诱导显示互惠性和强烈的相关性与相移的公开节奏。因此，在黑暗表达的定相和对光的反应方面，mPer 1与脉孢菌时钟基因frq相似。在SCN内，似乎有本地化的诱导现象mPer1，这表明两种类型的时钟（光响应和光无响应）被定位在这个昼夜节律中心。少

项目成果

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)

海老原史樹文: "生物時計の分子生物学"シュプリンガー・フェアラーク東京. 201 (1999)

Fumiaki Ebihara：“生物钟的分子生物学”Springer-Verlag 东京 201 (1999)。

Shigeyoshi Y.: "Coexistence of preprosomatostatin and preprotachykinin A mRNA in neurons of the rat suprachiasmatic nucleus."Mol.Brain Res.. 48巻. 159-163 (1997)

Shigeyoshi Y.：“大鼠视交叉上核神经元中前促生长素抑制素和前速激肽 A mRNA 的共存。”Mol.Brain Res. Vol. 48. 159-163 (1997)

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

Tei H, Okamura H, Shigeyoshi, Y., Fukuhara C, Ozawa R, Hirose M, Sakaki Y: "Circadian oscillation of a mammalian homologue of the Drosophila period gene"Nature. 389. 512-516 (1997)

Tei H，Okamura H，Shigeyoshi，Y.，Fukuhara C，Ozawa R，Hirose M，Sakaki Y：“果蝇周期基因的哺乳动物同源物的昼夜节律振荡”自然。