Presenilin-1/2双基因条件性敲除小鼠作为阿尔兹海默病动物模型的研究进展

Presenilin-1/2conditional double knockout mice: an ideal model for Alzheimer's disease

阿尔兹海默病(Alzheimer's disease,AD)是最普遍、危害最为严重的神经系统退行性疾病,迄今为止其发病机制尚未完全明确。越来越多的证据表明,presenilin-1/2的突变是遗传性AD主要的致病因素。利用条件性基因敲除技术构建的presenilin-1/2双基因条件性敲除小鼠(presenilin1 and presenilin 2 condi-tional double knockout mice,DKO小鼠),从脑的分子变化、组织形态、炎症反应、电生理特征以及整体动物的认知与情绪行为等多方面,模拟出了临床AD患者随时间发展的发病进程,同时用丰富环境(environment en-richment,EE)、能量限制(calories restriction,CR)、运动、药物等也能一定程度地改善该模型小鼠的学习记忆能力、情绪反应及分子病理学上的变化,这些研究结果提示DKO小鼠是一种较为理想的用于探明AD病因、研究病理过程以及筛选防治AD新药的动物模型。

Alzheimer＇s disease （AD） is the most common and serious neurodegenerative disease, whose molecular mechanism is still unclear. So far more and more evidences have shown that the mutation of presenilin 1/2 gene is the most important factor in familial AD. Presenilinl and presenilin 2 conditional double knockout mice （ DKO mice） , possess most clinical features of AD and exhibit molecular changes, morphology and neuropathology alteration, inflammatory reaction, electrophysiology, cognitive deficits and emotional response in gradually time-de- pendent mode ; furthermore, by environment enrichment（EE） , calories restriction （CR） , exercise and pharmacolo- gy, the deficits of the DKO mice in learning and memory ability, emotional response and neuropathology could be partially improved. All these results suggest that the DKO mice are an ideal AD animal model for exploring the pathologic causes of AD and screening new drugs for prevention and treatment of AD.