| APP695K595N/M596L突变转基因小鼠的建立和病理表型动态分析 |
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| 引用本文： | 王冬梅,李万波,袁树民,全雄志,张海涛,马春梅,曹兴水,张连峰.APP695K595N/M596L突变转基因小鼠的建立和病理表型动态分析[J].中国比较医学杂志,2011,21(12):5-9,25,94. |
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| 作者姓名： | 王冬梅 李万波 袁树民 全雄志 张海涛 马春梅 曹兴水 张连峰 |
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| 作者单位： | 中国医学科学院北京协和医学院医学实验动物研究所,卫生部人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室,北京 100021 |
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| 基金项目： | 卫生部项目，十一五新药专项支持 |
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| 摘 要： | 目的建立APP695K595N/M596L(Swedish突变)转基因小鼠和评价痴呆表型的发生和发展过程。方法将APP695K595N/M596L突变基因插入到小鼠朊蛋白(mouse prion protein)启动子下游,构建转基因表达载体,通过显微注射法建立APP695K595N/M596L突变转基因C57BL/6J小鼠。PCR鉴定转基因小鼠的基因表型,Western blotting检测APP突变基因表达。Thioflavin-S染色检测不同年龄转基因小鼠大脑病理改变。Morris水迷宫动态观察小鼠行为学改变。结果建立了人APP695K595N/M596L转基因小鼠,Thioflavin-S染色显示转基因小鼠9月龄时在脑海马区可检测到老年斑形成,并且在11、12月龄时明显增多。Morris水迷宫结果发现与同月龄野生型小鼠相比,该转基因小鼠5月龄开始出现学习记忆能力缺陷,7、9、11月行为学结果证实转基因小鼠的学习记忆能力缺陷随年龄增加而日趋严重(P<0.05)。结论建立了人APP695K595N/M596L转基因小鼠,并能再现人类阿尔茨海默症的行为学及神经病理学特征,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。
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| 关 键 词： | 朊蛋白 APP瑞士突变 转基因小鼠 水迷宫 |
Establishment of APP695swedishTransgenic Mouse Model and Analysis of the Development of Pathological Phenotypes |
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| WANG Dong-mei,LI Wan-bo,YUAN Shu-min,QUAN Xiong-zhi,ZHANG Hai-tao,MA Chun-mei,CAO Xing-shui,ZHANG Lian-feng.Establishment of APP695swedishTransgenic Mouse Model and Analysis of the Development of Pathological Phenotypes[J].Chinese Journal of Comparative Medicine,2011,21(12):5-9,25,94. |
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| Authors: | WANG Dong-mei LI Wan-bo YUAN Shu-min QUAN Xiong-zhi ZHANG Hai-tao MA Chun-mei CAO Xing-shui ZHANG Lian-feng |
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| Affiliation: | WANG Dong-mei,LI Wan-bo,YUAN Shu-min,QUAN Xiong-zhi,ZHANG Hai-tao,MA Chun-mei,CAO Xing-shui,ZHANG Lian-feng(1.Key Laboratory of Human Disease Comparative Medicine,Ministry of Health,2.Key Laboratory of Human Disease Animal Models,State Administration of Traditional Chinese Medicine,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences & Comparative Medical Center,Peking Union Medical College,Beijing 100021,China) |
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| Abstract: | Objective To generate a transgenic mouse line expressing human APP695K595N/M596L(Swedish mutation) and establish a transgenic Alzheimer disease model.Methods The transgenic plasmid was constructed by inserting the mutated APP695K595N/M596L gene into the downstream of mouse prion protein promoter.The transgenic mice were produced by microinjection and the genotype was detected by PCR.The gene expression levels were determined by Western blotting.The senile plaques were detected by thioflavin-S staining and v... |
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| Keywords: | Prion APP swedish mutant Transgenic mouse Water maze |
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