目的:构建与鉴定NDRG2基因全身敲除的阿尔茨海默症(AD)小鼠模型。方法:将NDRG2-/-、APP/PS1进行饲养杂交繁殖,将通过PCR技术鉴定基因型为NDRG2+/-APP/PS1的子一代小鼠再与NDRG2-/-小鼠回交获得子二代小鼠,提取子二代小鼠的基因组DNA再利用PCR方法:扩增NDRG2和APP/PS1基因片段并进行琼脂糖凝胶电泳检测获得4种基因型的小鼠。结果:选取基因型为NDRG2-/-APP/PS1的小鼠即为全身NDRG2敲除且淀粉样蛋白基因过表达的阿尔茨海默症模型小鼠。应用PCR方法:鉴定NDRG2基因全身敲除的AD小鼠模型。成功获得NDRG2基因全身敲除的AD小鼠,该基因型小鼠有繁殖能力,其繁殖符合孟德尔遗传规律。结论:成功构建NDRG2基因敲除的阿尔茨海默症模型小鼠,为进一步研究NDRG2基因在阿尔茨海默症病理发展过程中的作用机制及新的治疗方法的研究提供模型基础。
Objective:To breed N-myc downstream regulated gene 2(NDRG2) conventional knockout AD mice.Methods:Two mouse models,namely NDRG2-/-and APP/PS1 were interbred,and the first-generation offsprings that through the use of PCR with the NDRG2+/-APP/PS1 genotype were backcrossed with NDRG2-/-to obtain the second-generation mice.Genomic DNA was extracted from the second-generation mice for PCR to amplify the NDRG2 and APP/PS1 gene fragments followed by agarose gel electrophoresis to verify their sizes and we obtained four different genotypes of mice.Results:The mice with the NDRG2-/-APP/PS1 genotype were selected as the NDRG2 conventional knockout AD mice.Tissue samples were collected from the mice for the expression of NDRG2 or APP/PS1 using PCR.Conclusion:Genotyping results showed APP/PS1 was expressing in the NDRG2 conventional knockout mice,suggesting successful establishment of NDRG2 conventional knockout AD mice.The mice we obtained were fertile,and their breeding pattern followed the laws of Mendelian inheritance.More important,it provides a model foundation for further study of gene NDRG2 in AD-related pathology and new therapy.