Comparison of the expression and toxicity of AAV2/9 carrying the human A53T α-synuclein gene in presence or absence of WPRE
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
Affiliations
Xiuping Sun
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China
Xuan Yu
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China
Ling Zhang
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China
Wenjie Zhao
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China
Manshi Wang
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China
Yu Zhang
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China
Xianglei Li
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China
Ran Gao
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China
Ludivine S. Breger
Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France
Sandra Dovero
Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France
Gregory Porras
Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France
Pierre-Olivier Fernagut
Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France; Université de Poitiers, Laboratoire de Neurosciences Expérimentales et Cliniques, INSERM UMR_S 1084, Poitiers, France
Benjamin Dehay
Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France
Erwan Bezard
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China; Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France; Corresponding author.
Chuan Qin
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Peking Union Medical College (PUMC) & Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS), Beijing, China; Corresponding author.
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.
