使用液相色谱-串联质谱法对阿尔茨海默病小鼠模型中的DNA甲基化和羟甲基化进行定量分析。

Quantification of DNA methylation and hydroxymethylation in Alzheimer's disease mouse model using LC-MS/MS.

作者信息

Huang Qionglin, Xu Simin, Mo Mingming, Yang Qingjin, Li Jian, Zhong Yu, Zhang Junjie, Zhang Lijian, Ye Xiaoxiao, Liu Zhou, Cai Chun

机构信息

Analysis Center, Guangdong Medical University, Zhanjiang, 524023, China.

Institute of Neurology, Affiliated Hospital, Guangdong Medical University, Zhanjiang, 524001, China.

出版信息

J Mass Spectrom. 2018 Jul;53(7):590-594. doi: 10.1002/jms.4194.

DOI:10.1002/jms.4194

PMID:29696733

Abstract

Ambiguous alteration patterns of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) involved in Alzheimer's disease (AD) obstructed the mechanism investigation of this neurological disorder from epigenetic view. Here, we applied a fully quantitative and validated LC-MS/MS method to determine genomic 5mC and 5hmC in the brain cortex of 3 month-aged (12, 15, and 18 month) AD model mouse and found significant increases of 5mC and 5hmC levels in different months of AD mouse when compared with age-matched wild-type control and exhibited rising trend from 12-month to 18-month AD mouse, thereby supporting genomic DNA methylation and hydroxymethylation were positively correlated with developing AD.

摘要

参与阿尔茨海默病（AD）的5-甲基胞嘧啶（5mC）和5-羟甲基胞嘧啶（5hmC）的模糊变化模式阻碍了从表观遗传学角度对这种神经疾病发病机制的研究。在此，我们应用一种经过全面定量验证的液相色谱-串联质谱（LC-MS/MS）方法，测定3月龄（12、15和18个月）AD模型小鼠大脑皮层中的基因组5mC和5hmC，发现与年龄匹配的野生型对照相比，AD小鼠在不同月龄时5mC和5hmC水平显著升高，并且从12月龄到18月龄的AD小鼠呈现上升趋势，从而支持基因组DNA甲基化和羟甲基化与AD的发展呈正相关。