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

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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https://www.hal.inserm.fr/inserm-03154753
Contributor : Benjamin Dehay Connect in order to contact the contributor
Submitted on : Monday, March 1, 2021 - 11:38:05 AM
Last modification on : Wednesday, October 20, 2021 - 3:22:20 AM
Long-term archiving on: : Sunday, May 30, 2021 - 7:54:07 PM

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Xiuping Sun, Xuan Yu, Ling Zhang, Wenjie Zhao, Manshi Wang, et al.. Comparison of the expression and toxicity of AAV2/9 carrying the human A53T α-synuclein gene in presence or absence of WPRE. Heliyon, Elsevier 2021, 7 (2), pp.e06302. ⟨10.1016/j.heliyon.2021.e06302⟩. ⟨inserm-03154753⟩

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