学术论文

      3 xTg-拟 AD小鼠脑内七种时钟基因启动子区甲基化分析

      Promoter methylation analysis of seven clock genes in the brain of 3xTg mice

      摘要:
      目的:应用新的动物模型,建立一种快速简便的方法检测7种主要时钟基因per1、per2、cry2、clock、npas2、bmal1和bmal2启动子区甲基化状态,探索阿尔茨海默症引起的生理节律紊乱机制。方法采用甲基化特异性PCR( MSP)法,检测15例3xTg拟阿尔茨海默症( Alzheimer’ s disease,AD)小鼠和15例转基因阴性对照小鼠全脑7种时钟基因启动子区CpG岛甲基化水平。结果在转基因阳性小鼠中检测到3例cry2基因、1例clock和1例bmal2时钟基因发生甲基化现象,在对照组小鼠中未检测到时钟基因甲基化。结论启动子区甲基化这种表观遗传学修饰参与节律基因表达的调控,可能是AD疾病中时钟节律紊乱发生的重要原因。
      Abstract:
      Objective To investigate whether abnormal CpG methylation contributes to circadian dysfunction in Alzheimer’ s disease. Methods We examined the methylation of clock promoters in the mice brain by using a methylation-specific polymerase chain reaction ( MSP) assay.Results Methylation was detectable in the cry2; clock and bmal2 promoters in model group, although the frequency is low.However no positive result was found in control group.Conclusion Our results show that the promoter methylation may contribute to changes in circadian rhythms in certain slave oscillators, but not a key point.
      作者: 包训杰 [1] 蔡彦宁 [2] 祝艳秋 [1] 杨翠翠 [1] 李林 [1] 张兰 [1]
      Author: Bao Xunjie [1] Cai yanning [2] Zhu Yanqiu [1] Yang Cuicui [1] Li Lin [1] Zhang Lan [1]
      作者单位: 首都医科大学宣武医院药物研究室,北京100053; 神经变性病教育部重点实验室,北京100053 首都医科大学宣武医院神经生物学研究室,北京100053; 神经变性病教育部重点实验室,北京100053
      刊 名: 首都医科大学学报 ISTICPKU
      年,卷(期): 2015, (6)
      分类号: Q78
      机标分类号: R74 R39
      在线出版日期: 2016年1月18日
      基金项目: .国家重大新药创制重大科技专项,北京市卫生系统高层次卫生技术人才,北京市教委新医药学科群(XK100270569)。 This study was supported by National Science and Technology Major Project for Essential Drug Research and Development,Beijing Health and Technical High-Level Personal Plan,New Medical Disciplines Project of Beijing Educa-tion Committee(XK100270569).