生物钟基因mPer2调控节律性免疫功能的机制研究
其他题名Exploring the Mechanism on Circadian Immune Regulation by Circadian Clock Gene mPer2
罗永伦
学位类型硕士
导师孙中生
2006-06-01
学位授予单位中国科学院心理研究所
学位授予地点心理研究所
关键词mPer2 生物钟 皮质酮 免疫节律 细胞毒性
摘要为了研究生物钟基因mPer2在机体免疫节律调控中的作用机制,本实验选用mPer2基因敲除小鼠作为研究对象,探索mPer2调控节律性免疫应答机制。本实验分别从两方面来对此开展实验研究:一方面,本实验分别在9AM与2PM两个不同的时间点给野生型和mPer2敲除(mPer2-/-)小鼠注射同等剂量大肠杆菌内毒素(lipopolysaccharide,LPS),系统研究了机体急性炎症抑制激素(皮质酮)、生物钟基因和皮质酮代谢关键调控酶基因(mStAR)的应激性表达。本实验发现,皮质酮和mStAR的应激性表达与机体的节律性免疫应答相一致。此外,本实验还通过定量PCR和荧光素酶报告系统方法证明,mStAR在小鼠肾上腺中是一个钟控基因。而且mPer2在调控mStAR的转录表达中起到负调控的作用。另一方面,本实验通过定量PCR的方法系统的研究了参与细胞毒性调控的11个关键基因在野生型和mPer2-/-型小鼠骨髓中的表达水平和时间表达规律。研究结果表明,在这11个关键基因中,Ly49C, Ly49I, 和Nkg2d在mPer2-/-小鼠骨髓中表达水平显著偏低。此外,Ly49C和Nkg2d在野生型小鼠骨髓中具有节律性表达,而它们的节律性表达在mPer2-/-小鼠中被打乱。由此推断,Ly49C和Nkg2d是两个候选钟控基因,而且mPer2在调控它们表达中是起到正调控的作用。综合本实验的研究,证明皮质酮,mStAR,Ly49C和Nkg2d是mPer2调控节律性免疫应答过程中的关键介导分子。
其他摘要This project was carried out with the aims to investigate the mechanism of circadian immune regulation by one of the core Clock gene, mPer2. To achieve this, we selected mPer2 knock out (mPer2-/-) mice as the optimal animal model. Two different approaches were performed. In the first approach, we injected WT or mPer2-/- mice with an equal dosage of lipopolysaccharide (LPS), and systematically measured serum corticosterone induction, expression of core Clock genes, as well as a key enzyme for corticosterone metabolism (mStAR) in adrenal gland. We found that the acute induction of corticosterone and mStAR were closely associated with the circadian immune response to LPS. Besides, real time quantitative PCR (q-PCR) and luciferase assay consistently showed that mStAR is a Clock controlled gene in adrenal gland, where its expression is negatively influenced by mPer2. In the second approach, expression level and circadian manner of 11 cytotoxicity regulation genes in WT or mPer2-/- mice bone marrow were measured by q-PCR in order to explore the candidate genes which could mediate the circadian immune regulation by mPer2. We found that expression level of Ly49C, Ly49I, and Nkg2d was significant down-regulated in mPer2-/- mice. Further, we found that daily expression of Ly49C and Nkg2d fluctuated in a circadian manner in WT mice, where these rhythms were disrupted in mPer2-/- mice. Thus, it was suggested that these two cytotoxic genes were two clock controlled genes whose circadian expression were regulated by mPer2. Taken together, our results suggested that corticosterone, mStAR, Ly49C, and Nkg2d were four candidate molecules that may mediate the circadian immune response regulation by mPer2.
页数62
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/4742
专题中国科学院心理研究所回溯数据库(1956-2010)
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罗永伦. 生物钟基因mPer2调控节律性免疫功能的机制研究[D]. 心理研究所. 中国科学院心理研究所,2006.
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