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Key Laboratory of Human Diseases Comparative Medicine,Ministry of Health;Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences(CAMS)&Comparative Medicine Centre,Peking Union Medical CoHege(PUMC) 在期刊界中查找 在百度中查找 在本站中查找
Objective In view of better performance of rat than mice in nervous diseases studies, to generate a transgenic Parkinson's disease rat line expressing alpha-synuclein gene with A53T mutation and provide a better PD animal model. Methods The transgenic plasmid was constructed by inserting the alpha-synuclein gene with A53T mutation into the downstream of mouse PDGF promoter. The transgenic rats were produced by microinjection and the genotype was detected by PCR. The protein expression levels in brain tissues were determined by western blotting. The expression of human alpha -synuclein in the brain tissues from transgenic rats was analyzed by immunohistochemistry staining(IHC) and immunofluorescence(IF).The changes of the number of tyrosine hydroxylase(TH)-positive neurons in the substantia nigra were observed by IHC and IF. The motor performances of transgenic rats were measured by rotating rod experiment and gait analysis system. Results One transgenic rat line with high human alpha-synuclein expression levels was established. Histopathological examination revealed the abnormal aggregation in midbrain dopamine (DA) neurons and significantly reduced number of TH-positive neurons (69%,P<0.05) in substantia nigra from transgenic rats. Rotating rod and rat gait analysis indicated declined motor performances(40% - 60%,P<0.05)) and gait disorder of transgenic rats. Conclusions The human a-synuclein A53T transgenic rat models of Parkinson’s disease were established.