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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2008-2-21
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pubmed:abstractText |
Mutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either wild-type human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of wild-type LRRK2. Treatment with l-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase-positive neurons. To our knowledge, this is the first in vivo"gain-of-function" model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-10332728,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-10704417,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-10746727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-11014814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-11805242,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-12555273,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-12971891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-14593171,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-14963491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-15541308,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-15541309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-15556931,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-15680455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-15680456,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-15680457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-16269541,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-16321986,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-16437559,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-16750377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-16966502,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-16980962,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17015234,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17060589,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17068789,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17114044,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17192723,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17344383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17447891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17498648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17584768,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17623048,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-17978026,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-3129458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-8223268,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18258746-8786384
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1091-6490
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pubmed:author |
pubmed-author:JiangHaibingH,
pubmed-author:JiaoYuchenY,
pubmed-author:LiXuepingX,
pubmed-author:LiuZhaohuiZ,
pubmed-author:MontellCraigC,
pubmed-author:MoranTimothyT,
pubmed-author:NBB,
pubmed-author:RenQiutingQ,
pubmed-author:RossChristopher ACA,
pubmed-author:SawaAkiraA,
pubmed-author:SmithWanli WWW,
pubmed-author:WangTaoT,
pubmed-author:WangXiaoyueX
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2693-8
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18258746-Animals,
pubmed-meshheading:18258746-Animals, Genetically Modified,
pubmed-meshheading:18258746-Disease Models, Animal,
pubmed-meshheading:18258746-Dopa Decarboxylase,
pubmed-meshheading:18258746-Dopamine,
pubmed-meshheading:18258746-Drosophila melanogaster,
pubmed-meshheading:18258746-Gait Disorders, Neurologic,
pubmed-meshheading:18258746-Gene Expression Regulation,
pubmed-meshheading:18258746-Microscopy, Electron,
pubmed-meshheading:18258746-Nerve Degeneration,
pubmed-meshheading:18258746-Parkinsonian Disorders,
pubmed-meshheading:18258746-Protein-Serine-Threonine Kinases,
pubmed-meshheading:18258746-Retina
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pubmed:year |
2008
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pubmed:articleTitle |
A Drosophila model for LRRK2-linked parkinsonism.
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pubmed:affiliation |
Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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