Abstract
X-linked IAP protein is a potent inhibitor of cell death. Here, we describe a novel transgenic mouse in which the human XIAP gene is expressed under the control of the neuron-specific enolase promoter (NSE-xiap). We demonstrate that nigrostriatal dopamine neurons of NSE-xiap mice were resistant to the damaging effects of the dopaminergic neurotoxin MPTP. MPTP-induced reduction of striatal dopamine metabolism was also attenuated in NSE-xiap mice. Furthermore, NSE-xiap mice treated with MPTP did not exhibit deficits in exploratory behaviour in an open-field test. Taken together, these findings suggest that strategies to enhance neuronal expression of XIAP may provide therapeutic benefit for the treatment of neurodegeneration in Parkinson's disease.
Copyright 2003 Elsevier Science (USA)
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
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Animals
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Behavior, Animal / drug effects
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Behavior, Animal / physiology
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Cell Death / drug effects
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Cell Death / genetics*
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Dopamine / metabolism
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Drug Resistance / genetics*
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Exploratory Behavior / drug effects
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Exploratory Behavior / physiology
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Immunohistochemistry
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Mice
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Mice, Transgenic
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Neostriatum / drug effects
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Neostriatum / metabolism
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Neostriatum / pathology
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Neural Pathways / drug effects
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Neural Pathways / metabolism
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Neural Pathways / pathology
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Neurons / drug effects
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Neurons / metabolism*
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Parkinsonian Disorders / genetics
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Parkinsonian Disorders / metabolism*
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Parkinsonian Disorders / therapy
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Phosphopyruvate Hydratase / genetics
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Promoter Regions, Genetic / genetics
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Proteins / genetics
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Proteins / metabolism*
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Substantia Nigra / drug effects
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Substantia Nigra / metabolism*
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Substantia Nigra / pathology
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X-Linked Inhibitor of Apoptosis Protein
Substances
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Proteins
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X-Linked Inhibitor of Apoptosis Protein
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Phosphopyruvate Hydratase
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Dopamine