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

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 nigros...

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Published in:Heliyon 2021-02, Vol.7 (2), p.e06302-e06302, Article e06302
Main Authors: Sun, Xiuping, Yu, Xuan, Zhang, Ling, Zhao, Wenjie, Wang, Manshi, Zhang, Yu, Li, Xianglei, Gao, Ran, Breger, Ludivine S., Dovero, Sandra, Porras, Gregory, Fernagut, Pierre-Olivier, Dehay, Benjamin, Bezard, Erwan, Qin, Chuan
Format: Article
Language:English
Subjects:
adults
asymmetry
disease models
gene expression
genes
humans
Life Sciences
males
mice
Mouse
Parkinson disease
Parkinson's disease
protein synthesis
serine
Synucleinopathy
toxicity
Woodchuck hepatitis virus
Woodchuck hepatitis virus post-transcriptional regulatory element
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Summary: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. Parkinson's disease; Synucleinopathy; Woodchuck hepatitis virus post-transcriptional regulatory element; Mouse.
ISSN:2405-8440
2405-8440
DOI:10.1016/j.heliyon.2021.e06302