mSOD1转基因阳性家族性肌萎缩侧索硬化症模型大鼠的生物学特征  

Biological characteristics of mSOD1 transgenic rat models of familial amyotrophic lateral sclerosis

作　　者：包建玲[1] 黄红云[1] 刘彦[1] 王洪美[1] 王援朝[1] 刘佳[1] 曹敬丽[1] 方明俊[1] 

机构地区：[1]北京市虹天济神经科学研究院,北京市石景山区西山神经再生和功能重建研究所,北京市100041

出　　处：《中国组织工程研究与临床康复》2007年第46期9301-9304,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：目的:家族性肌萎缩侧索硬化症转基因大鼠模型的鉴定及生物学特性的检测。方法:实验于2006-06/12在北京市虹天济神经科学研究院完成。从国外购来mSOD1转基因的肌萎缩侧索硬化症大鼠模型及其野生型进行繁殖扩增;PCR筛选mSOD1基因阳性鼠作为实验观察对象;观察其行为学变化、绘制生长曲线;记录神经传导速度及肌电情况;苏木精-伊红染色法观察股二头肌标本病理学变化;尼氏染色法进行中枢神经系统的神经元计数。实验过程中对动物的处置符合动物伦理学标准。结果:繁殖并扩增了肌萎缩侧索硬化症模型的种群;PCR法成功筛选出了mSOD1基因的阳性鼠,mSOD1阳性鼠在生长过程中逐渐出现四肢运动障碍、体质量急剧降低且很快死亡;发病鼠神经传导速度减慢、肌电显示出自发的纤颤电位;肌纤维发生萎缩;中枢神经系统的神经元丢失明显且有部分神经元发生空泡样变。结论:mSOD1转基因阳性的肌萎缩侧索硬化症模型大鼠可表现出与人类疾病的相似症状,生物学各项指标变化明显,是理想的肌萎缩侧索硬化症研究模型。AIM： To detect and investigate the biologic characteristics of the transgenic rat model of familial amyotrophic lateral sclerosis （FALS） expressing human SODIG93A mutation. METHODS： The experiment was performed at the Beijing Hongtianji Neuroscience Academy from June to December 2006. The transgenic rat models of ALS and wild-type rats were bought from abroad and breed. The expression of the mSOD1 gene was examined by polymerase chain reaction （PCR） assay. The abnormality was detected to observe ethology assay and draw survivor curve. Nerve conduction velocity and myoelectricity were recorded. Pathological change of biceps femoris was observed by hematoxylin-eosin （HE） staining. Neuron of central nervous system was stained by Nissrs staining. The intervention was according to the animal ethical standard. RESULTS： The transgenic rat model of ALS expressing human SOD1G93Amutation was amplified. The rats expressing mSOD1 was found by PCR. The positive rats develop motor neuron disease and body mass decreased rapidly. Abnormal electromyography （EMG） and slow nerve conductions was found from onset of motor neuron disease. Leg muscles revealed obvious atrophic myofibers. Motor neuron loss appeared within this disease and partial neurons had vacuole change. CONCLUSION： The transgenic rat models of ALS expressing human SOD1G93A mutation is an ideal ALS model,and they provide a valuable resource to therapeutic experimentation.

关 键 词：肌萎缩侧索硬化症 超氧化物歧化酶1 转基因大鼠 

分 类 号：R746.4[医药卫生—神经病学与精神病学]