APP／PS双转基因阿尔茨海默病小鼠模型的老年斑及行为学动态分析

目的研究APP／PS1双转基因阿尔茨海默病小鼠模型老年斑形成和行为改变的动态过程。方法将转APPswe突变基因小鼠与转PSAE9基因突变小鼠杂交，PCR鉴定APPswe／PSAE9双突变转基因小鼠的基因表型，筛选阳性小鼠建立APPswe／PS／kE9双转基因C57BL／6J小鼠模型。抗邮免疫组化、改良Bieschowsky银染法、Thioflavin-S荧光分别动态检测3、4、5、6、9、12月龄APPswe／PSAE9双转基因小鼠大脑病理改变。荷兰Noldus公司EthovisionXT监测分析软件动态观察3、6、9月龄的APPswe／PSAE9双转基因小鼠Morris水迷宫行为学改变。利用SPSS16．0软件统计分析。结果建立了人APPswe／PSAE9双转基因阿尔茨海默病小鼠模型。3月龄APP／PS1双转基因小鼠大脑组织抗Aβ1—17免疫组织化学、改良Bieschowsky银染法、Thioflavin—S荧光未检测到有明显老年斑形成。4．5月龄APPswe／PSAE9双转基因小鼠大脑组织上述三种方法均可检测到老年斑。9、12月龄双转基因小鼠老年斑数量体积明显增加，出现与阿尔茨海默病患者较相似的老年斑改变。Morris水迷宫试验发现3、6、9月龄APPswe／PSAE9双转基因小鼠行为学结果与同月龄野生型小鼠有差异，说明与同月龄野生型小鼠相比出现记忆学习能力缺陷（P〈0．05）。结论成功建立了人APPswe／PSAE9双转基因小鼠阿尔茨海默病模型，为阿尔茨海默病发病机制研究和药物研发提供了有价值的动物模型。

Continuous Analysis of Senile Plaque and Behaviour In APPswe/PSAE9 Double-transgenic Gene Mouse Model of Alzheimer Disease

Objective To research senile plaque formation and behaviour change process in APPswe/PS△E9 double- transgenicgene mouse model of Alzheimer disease. Methods Crossbreed the transgenic APPswe gene and transgenic PS△E9 gene mouse models of Alzheimer disease to produce APPswe/PSAE9 double-transgenic gene mouse. The genotype of APPswe/PS△E9 double-trausgenie mice were detected by PCR and establish APPswe/PS△E9 double-transgenic C57BL/6J mouse model of Alzheimer disease. Detection senile plaque formation in 3,4,5,6,9,12 months old mouse brain tissue by immunohistochemistry, modification Biesehowsky silver stain and Thioflavin-S Stain. Behaviour tests of 3,6,9 months old mouse was determined by Morris water maze trials. Results The transgenic APPswe/ PSAE9 double-transgenic gene C57BL/6J mouse model of Alzheimer disease were established. 3 month old mouse can detect behaviour change and 4.5 month old mouse can detect senile plaque formation .senile plaque of 9 - 12 month old mouse was similar with the plaque of Alzheimer disease patients, spatial memory deficits of 6-9 month old mouse can be observed（ P 〈 0.05 ）. Conclusions The obvious senile plaque can be detected in brain tissue of 4.5 months old mouse and spatial memory deficits can occur in 3 months old mouse, indicating that the APPswe/PS~E9 gene transgenic mouse is a useful animal model of AD in Alzheimer disease pathology and medicament research.