阿尔茨海默病presenilin-1/presenilin-2双基因敲除小鼠海马Ptprd基因甲基化改变

Methylation change of Ptprd gene in hippocampus of presenilin-1/presenilin-2 conditional double knockout mice with Alzheimer's disease

目的探讨Ptprd基因在中期阿尔茨海默病小鼠模型(presenilin-1/presenilin-2条件性双基因敲除小鼠,d KO小鼠)海马组织甲基化改变情况。方法取12月龄雌性d KO小鼠3只和12月龄雌性CBAC57小鼠3只分别作为实验组和对照组,采用第二代高通量测序技术(简化的代表性亚硫酸氢盐测序,RRBS)检测其小鼠海马组织基因组DNA,然后将测序后的结果过滤并用Bismark(v O.7.4)软件进行比对分析以获取异常甲基化基因。结果二代高通量测序法筛选出的Ptprd基因在中期阿尔兹海默病程中呈低甲基化改变(P<0.05)。结论在中期AD d KO小鼠模型中可能出现了Ptprd基因低甲基化,低甲基化Ptprd基因可能与AD的中期病程有关。

Objective To investigate the methylation change status of Ptprd gene in hippocampus tissues of presenilin-1/presenilin-2 conditional model knockout mice（d KO mice） with Alzheimer disease（AD）. Methods Three female d KO mice and three female CBAC57 mice of 12 month old were taken as the experimental group and the control group respectively. The genomic DNA of the hippocampus of the mice was detected by the second generation high throughput sequencing technology（reduced representation bisulfite sequencing, RRBS）, and then the results were compared and analyzed by Bismark（v O.7.4） software. Then the abnormal methylation gene were got. ResultsThe Ptprd gene was selected by second generation high throughput sequencing technology, it showed hypo methylation changed in the middle-term course of Alzheimer＇s disease（P〈0.05）. Conclusion The hypo methylation of the Ptprd gene in the d KO mouse model at the medium-term course of AD. And that suggests that the hypomethylation of the Ptprd gene may be involved in the medium-term course of AD.