阿尔茨海默病转基因动物模型:如何更接近病理特征?

Alzheimer's disease transgenic animal models: How to get more similar pathological characteristics?

背景:目前阿尔茨海默病的病因、发病机制还不是十分清楚,很大程度上制约了阿尔茨海默病治疗药物的筛选,而主要障碍之一是缺少合适的动物模型。日趋成熟的转基因动物技术可以在活体上研究某一特定致病基因的作用,已成为阿尔茨海默病较为理想的动物模型。目的:综述近几年国内外阿尔茨海默病转基因动物模型的研究进展。方法:第一作者应用计算机检索2013年7月以前PubMed数据库、中国期刊全文数据库有关阿尔茨海默病转基因动物模型的文章,英文检索词为"Alzheimer’s disease,transgenic mouse,Animal model,dementia",中文检索词为"阿尔茨海默病,转基因动物,动物模型,痴呆"。最终选择41篇文献进行综述。结果与结论:阿尔茨海默病的病因是多元性的,遗传因素是其中的一个重要因素。现有的阿尔茨海默病转基因动物模型,包括单转基因模型、双转基因模型以及多重转基因模型。单转基因动物模型是通过重组DNA技术,将某一种突变的外源性基因片段整合到动物的基因组中,该模型只能研究阿尔茨海默病某一特定的病理变化;双转基因动物模型是通过重组DNA技术将两种外源性突变基因同时转染动物,相比单转基因模型,其病理变化与阿尔茨海默病更加吻合,但是仍然不能完全模拟疾病;多重转基因模型是利用不同的转基因鼠杂交或多个基因同时转入等方法,得到的多重转基因模型,该模型能更好的模拟临床阿尔茨海默病的发病过程和病理特征,但存在近亲衰退等缺点。各种动物模型都有其优点,但也存在着缺点,还需进一步建立更为完善的阿尔茨海默病转基因动物模型,更准确、完整地再现阿尔茨海默病的病理特征。

BACKGROUND： Alzheimer＇s disease causes and pathogenesis remain unclear, which greatly restrict the screening of drugs. And the main reason is lack of suitable animal models. The developing transgenic animal technology allows studying the role of certain pathogenic gene in vivo, and has regarded the ideal animal models for Alzheimer＇s disease. OBJECTIVE： To summarize the research advance of Alzheimer＇s disease transgenic animal models. METHODS： Using ＂Alzheimer＇s disease, transgenic mouse, animal model, dementia＂ in Chinese and English as the key words, the first author retrieved PubMed and CNKI databases published before July 2013. Finally, 41 articles were included in result analysis. RESULTS AND CONCLUSION： The etiology of Alzheimer＇s disease is diverse, and genetic factor is one important factor. The existing transgenic animal models of Alzheimer＇s disease include single genetically modified models, double genetically modified models and multiple transgenic models. Single transgenic animal models can make a kind of mutated exogenous gene integrate into the genomes of animals by using recombinant DNA technology. This kind of models can be applied to only study one specific pathological change of Alzheimer＇s disease. Double transgenic animal models can make two kinds of mutated exogenous gene integrate into the genomes of animals and simultaneously transfect animals by using recombinant DNA technology. This kind of models is closer to the pathological changes of Alzheimer＇s disease than single transgenic animal models, but still cannot simulate Alzheimer＇s disease. Multiple genetically modified models are obtained with different transgenic mice hybridization or several genes transfection, which are most similar to clinical process and pathological features of AIzheimer＇s disease. However, this kind of models may develop a decline in consanguinity. Each kind of animal model has their advantages and shortcomings, and a better transgenic animal model is urgently needed to completely simulate pathological characteristics of Alzheimer＇s disease.