Dusonchet, J.Kochubey, O.Stafa, K.Young, S. M.Zufferey, R.Moore, D. J.Schneider, B. L.Aebischer, P.2011-01-202011-01-202011-01-20201110.1523/JNEUROSCI.5092-10.2011https://infoscience.epfl.ch/handle/20.500.14299/63166WOS:000286373700015The 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.Adenoviral VectorsMiceExpressionBraintext::journal::journal article::research article