Comparison of the expression and toxicity of AAV2/9 carrying the human A53T α-synuclein gene in presence or absence of WPRE

存在或不存在 WPRE 的情况下携带人类 A53T α-突触核蛋白基因的 AAV2/9 的表达和毒性比较

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作者:Xiuping Sun, Xuan Yu, Ling Zhang, Wenjie Zhao, Manshi Wang, Yu Zhang, Xianglei Li, Ran Gao, Ludivine S Breger, Sandra Dovero, Gregory Porras, Pierre-Olivier Fernagut, Benjamin Dehay, Erwan Bezard, Chuan Qin

Abstract

Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) is thought to enhance transgene expression of target genes delivered by adeno-associated viral (AAV) vectors. This study assessed the protein expression of α-synuclein, phosphorylated α-synuclein at Serine 129, extent of nigrostriatal degeneration as well as subsequent behavioral deficits induced by unilateral intranigral stereotactic injection in male adult C57BL/6J mice of an AAV2/9 expressing A53T human α-synuclein under the control of the synapsin promoter in presence or absence of the WPRE. The presence of WPRE enabled to achieve greater nigrostriatal degeneration and synucleinopathy which was concomitant with worsened forelimb use asymmetry. This work refines a mouse Parkinson's disease model in which anatomo-pathology is related to behavioral deficits.

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