用于帕金森氏症研究的GFAP-DsRed转基因巴马小型猪模型构建

猪是生物医学研究良好模型，转基因猪是人类特定疾病研究的转化生物医学重要大动物模型。帕金森氏症是一种渐进神经退行性变疾病，其研究需能对其病理进程进行示踪的大动物模型，目前国内外尚无用于帕金森氏症研究的转基因猪模型。本项目选用广西巴马小型猪为材料，利用繁殖生物技术，构建GFAP-DsRed表达载体，通过体细胞核移植生产转基因胚胎、进行胚胎移植，获得在中枢神经系统(CNS)特异表达红色荧光蛋白(DsRed)的转基因巴马小型猪，繁殖并选育出第二代GFAP-DsRed转基因巴马小型猪，利用神经毒素处理该第二代转基因巴马小型猪进行帕金森氏症研究，最终开发出用于帕金森氏症研究的转基因巴马小型猪模型。该模型特色在于通过追踪DsRed在CNS表达情况判断CNS受损害程度，为帕金森氏症研究提供新工具。本项目还将丰富小型猪繁殖学领域的技术和理论，同时为具有重要经济价值的广西地方猪品种的保种和品种改良开辟新途径。

The pig is a good model for biomedical research and transgenic pig is an important big animal model for translational biomedical research on particular human diseases. Parkinson's disease is a progressive neurodegenerative disease and the research of it needs big animal models of which pathological process can be tracked. At present there is not any transgenic pig model for studying Parkinson's disease. In this project Guangxi Bama minipig and reproductive biotechnology are used. The GFAP-DsRed expression vector is constructed and transfected into Bama minipig somatic cells, and transgenic embryos are produced using somatic cell nuclear transfer technique and transferred into recipient pigs. A batch of transgenic Bama minipigs expressing DsRed specifically in central nervous system will be obtained and the second generation of GFAP-DsRed transgenic Bama minipig will also be obtained. The second generation of transgenic Bama minipig will be then used for studying Parkinson's disease by being treated with neurotoxicant to induce Parkinson's disease and a transgenic Bama minipig model for studying Parkinson's disease will be developed at the end of this project. The distinguishing feature of this transgenic Bama minipig model is that the degree of damage of central nervous system can be judged by tracking the expression status of DsRed in central nervous system thus provide a new tool for studying Parkinson's disease. This project will also enrich the technologies and theory in minipig reproduction and open new ways for protection and improvement of Guangxi local pig breeds with important variety and economic value.