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

Heliyon (Feb 2021)

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.

Journal volume & issue: Vol. 7, no. 2
p. e06302

Abstract

Read online

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.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

About the journal

Abstract

Keywords