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- Title
A Rat Model of Progressive Nigral Neurodegeneration Induced by the Parkinson's Disease-Associated G2019S Mutation in LRRK2.
- Authors
Dusonchet, Julien; Kochubey, Olexiy; Stafa, Klodjan; Young Jr., Samuel M.; Zufferey, Romain; Moore, Darren J.; Schneider, Bernard L.; Aebischer, Patrick
- Abstract
The G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene is the most common genetic cause of Parkinson's disease (PD), accounting for a significant proportion of both autosomal dominant familial and sporadic PD cases. Our aim in the present study is to generate a mammalian model of mutant G2019S LRRK2 pathogenesis, which reproduces the robust nigral neurodegeneration characteristic of PD. We developed adenoviral vectors to drive neuron-specific expression of full-length wild-type or mutant G2019S human LRRK2 in the nigrostriatal system of adult rats. Wild-type LRRK2 did not induce any significant neuronal loss. In contrast, under the same conditions and levels of expression, G2019S mutant LRRK2 causes a progressive degeneration of nigral dopaminergic neurons. Our data provide a novel rat model of PD, based on a prevalent genetic cause, that reproduces a cardinal feature of the disease within a rapid time frame suitable for testing of neuroprotective strategies.
- Subjects
NEURODEGENERATION; LABORATORY rats; LEUCINE; PARKINSON'S disease; ANIMAL models in research; NEUROPROTECTIVE agents; GENETIC mutation
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 3, p907
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5092-10.2011