Abstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. We created a LRRK2 transgenic mouse model that recapitulates cardinal features of the disease: an age-dependent and levodopa-responsive slowness of movement associated with diminished dopamine release and axonal pathology of nigrostriatal dopaminergic projection. These mice provide a valid model of Parkinson's disease and are a resource for the investigation of pathogenesis and therapeutics.
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Acknowledgements
We wish to thank K. Merchant and her team at Eli Lilly and Company for generating the immunoblot data that facilitated selection of transgenic lines, S. Fleming and M.-F. Chesselet for advice on behavioral studies, and X. William Yang and A. Yamamoto for insightful discussions. This work was supported in part by grants from the Michael J. Fox Foundation and the US National Institutes of Health to C.L., from the Department of Defense to M.F.B., and from US National Institutes of Health and the Parkinson's Disease Foundation to R.E.B. and T.F.O.
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Supplementary Text and Figures
Supplementary Figures 1–7 and Supplementary Methods (PDF 7201 kb)
Supplementary Video 1
Home cage behavior of 10-month-old wild-type nontransgenic littermates that moved normally, and LRRK2R1441G BAC transgenic mice that became immobile (akinesia-like). The movie is real time. (AVI 1582 kb)
Supplementary Video 2
Open field tests of 10-month-old wild-type nontransgenic littermates that moved normally. (AVI 2446 kb)
Supplementary Video 3
Open field tests of 10-month-old LRRK2R1441G BAC transgenic mice that became immobile. (AVI 1563 kb)
Supplementary Video 4
Cylinder test of 10-month-old wild-type nontransgenic littermates that moved and reared normally. (AVI 1500 kb)
Supplementary Video 5
Cylinder test of 10-month-old LRRK2R1441G BAC transgenic mice that became immobile. (AVI 557 kb)
Supplementary Video 6
Rescue of the motor deficit in LRRK2R1441G BAC transgenic mice by levodopa. Home cage behavior of 10-month-old LRRK2R1441G BAC transgenic mice about 1.5 h post levodopa injection. There was a significant increase of motor activity. The movie is real time. (AVI 987 kb)
Supplementary Video 7
Rescue of the motor deficit in LRRK2R1441G BAC transgenic mice by levodopa. Open field test of 10-month-old LRRK2R1441G BAC transgenic mice about 40 min post levodopa injection. There was a significant increase of motor activity. The movie is real time. (AVI 2092 kb)
Supplementary Video 8
Rescue of the motor deficit in LRRK2R1441G BAC transgenic mice by levodopa. Cylinder test of 10-month-old LRRK2R1441G BAC transgenic mice about 1 h post levodopa injection. There was a significant increase of motor activity. The movie is real time. (AVI 2092 kb)
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Li, Y., Liu, W., Oo, T. et al. Mutant LRRK2R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat Neurosci 12, 826–828 (2009). https://doi.org/10.1038/nn.2349
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DOI: https://doi.org/10.1038/nn.2349
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