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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Age Factors
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Animals
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Antiparkinson Agents / therapeutic use
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Apomorphine / therapeutic use
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Brain / drug effects
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Brain / pathology
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Brain / physiopathology
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Chromosomes, Artificial, Bacterial
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Disease Models, Animal*
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Dopamine / metabolism
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Dopamine Uptake Inhibitors / pharmacology
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Gene Transfer Techniques
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Humans
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Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
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Levodopa / therapeutic use
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Mice
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Mice, Transgenic*
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Movement Disorders / drug therapy
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Movement Disorders / genetics
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Mutation, Missense
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Neurons / pathology
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Neurons / physiology
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Nomifensine / pharmacology
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Parkinson Disease* / genetics
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Parkinson Disease* / pathology
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Parkinson Disease* / physiopathology
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
Substances
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Antiparkinson Agents
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Dopamine Uptake Inhibitors
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Nomifensine
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Levodopa
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LRRK2 protein, human
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Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
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Protein Serine-Threonine Kinases
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Apomorphine
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Dopamine