建立阿尔茨海默症的转基因动物模型  

ESTABLISHMENT OF THE TRANSGENIC MODEL OF ALZHEIMER DISEASE

作　　者：常洋[1] 秦川[1] 尹红星[1] 朱华[1] 蔡有余[1] 

机构地区：[1]中国医学科学院中国协和医科大学实验动物研究所,北京100021

出　　处：《解剖学报》2000年第2期144-147,I010,共5页Acta Anatomica Sinica

基　　金：国家科技部特别资助

摘　　要：目的　建立阿尔茨海默症转基因动物模型 ,为病因研究和药物筛选提供了一个合适的动物模型。　方法　通过显微注射方法将外源 DNA注射到小鼠受精卵的雄性原核 ,移植到假孕母鼠的输卵管。仔鼠出生后 ,经PCR及 PCR- Southern杂交检测阳性小鼠。　结果　共注射 887枚受精卵 ,存活 482枚 ,移卵后产仔 35只 ,阳性 3只。阳性鼠分别传代 ,在 F2代获得纯合子后建系。免疫组织化学显示在大脑皮层、小脑及海马的神经细胞有 Aβ沉淀形成。　结论　通过显微注射的方法已建立与人类发病机理相似的阿尔茨海默症转基因动物模型。Objective\ To establish a transgenic model of Alzheimer disease. Methods\ We constructed the transgene containing the human APP cDNA 695 V717I driven by PDGF promoter which expresses specifically in nervous system. The transgene was microinjected into the male pronucleus of the zygotes. The tail DNA of pups was tested by PCR and Southern blot. Results\ 887 embryos were microinjected, 482 were implanted to 20 recipient pseudopregnant mice, 3 of 35 pups carrying the transgene. Each Heterozygous founders generated a transgenic line that was homozygous for the transgene. Immunocytochemistry revealed plaques in pallium, cerebellum, and hippocampus. Conclusions\ Resembling animal model of the human pathogenic mechanism for the screening of proper remedies established in our laboratory and could be used for further studied.

关 键 词：APP 转基因 动物模型 早老性痴呆 

分 类 号：R149.16[医药卫生—军事预防医学]