Journal article
A Rat Model of Progressive Nigral Neurodegeneration Induced by the Parkinson's Disease-Associated G2019S Mutation in LRRK2
The Journal of neuroscience, Vol.31(3), pp.907-912
01/19/2011
DOI: 10.1523/JNEUROSCI.5092-10.2011
PMCID: PMC6632940
PMID: 21248115
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.
Details
- Title: Subtitle
- A Rat Model of Progressive Nigral Neurodegeneration Induced by the Parkinson's Disease-Associated G2019S Mutation in LRRK2
- Creators
- Julien Dusonchet - Neurodegenerative Studies LaboratoryOlexiy Kochubey - Laboratory of Synaptic Mechanisms, andKlodjan Stafa - Laboratory of Molecular Neurodegenerative Research, Brain Mind Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland, andSamuel M Young - Max Planck Florida Institute for Integrative Biology and Neuroscience, Jupiter, Florida 33458Romain Zufferey - Neurodegenerative Studies LaboratoryDarren J Moore - Laboratory of Molecular Neurodegenerative Research, Brain Mind Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland, andBernard L Schneider - Neurodegenerative Studies LaboratoryPatrick Aebischer - Neurodegenerative Studies Laboratory
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.31(3), pp.907-912
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.5092-10.2011
- PMID
- 21248115
- PMCID
- PMC6632940
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 01/19/2011
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
- Record Identifier
- 9984025454902771
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