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Reference Report
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| Citation | Liu, Z., Wang, X., Yu, Y., Li, X., Wang, T., Jiang, H., Ren, Q., Jiao, Y., Sawa, A., Moran, T., Ross, C.A., Montell, C., Smith, W.W. (2008). A Drosophila model for LRRK2-linked parkinsonism. Proc. Natl. Acad. Sci. U.S.A. 105(7): 2693--2698. (Export to RIS) | ||
| FlyBase ID | FBrf0204181 | ||
| Publication Type | Research paper | ||
| PubMed ID | 18258746 | ||
| PubMed Abstract | 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. | ||
| DOI | 10.1073/pnas.0708452105 | ||
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| Language of Publication | English | ||
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| Publication Type | Journal | ||
| Abbreviation | Proc. Natl. Acad. Sci. U.S.A. | ||
| Title | Proceedings of the National Academy of Sciences of the United States of America | ||
| Publication Year | 1915- | ||
| ISBN/ISSN | 0027-8424 | ||
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Data from Reference
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| Alleles (5)
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| Constructs (5)
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| Genes (6)
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