Comparison of the expression and toxicity of AAV2/9 carrying the human A53T α-synuclein gene in presence or absence of WPRE
Heliyon. 2021-02-01; 7(2): e06302
DOI: 10.1016/j.heliyon.2021.e06302
Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) is thought to enhance transgeneexpression of target genes delivered by adeno-associated viral (AAV) vectors. This study assessed the proteinexpression ofα-synuclein, phosphorylatedα-synuclein at Serine 129, extent of nigrostriatal degeneration as wellas subsequent behavioral deficits induced by unilateral intranigral stereotactic injection in male adult C57BL/6Jmice of an AAV2/9 expressing A53T humanα-synuclein under the control of the synapsin promoter in presence orabsence of the WPRE. The presence of WPRE enabled to achieve greater nigrostriatal degeneration and synu-cleinopathy 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.