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Lack of nigral pathology in transgenic mice expressing human alpha-synuclein driven by the tyrosine hydroxylase promoter.

Neurobiology of disease | Jun 9, 2001

http://www.ncbi.nlm.nih.gov/pubmed/11442360

alpha-Synuclein has been identified as a major component of Lewy body inclusions, which are one of the pathologic hallmarks of idiopathic Parkinson's disease. Mutations in alpha-synuclein have been found to be responsible for rare familial cases of Parkinsonism. To test whether overexpression of human alpha-synuclein leads to inclusion formation and neuronal loss of dopaminergic cells in the substantia nigra, we made transgenic mice in which the expression of wild-type or mutant (A30P and A53T) human alpha-synuclein protein was driven by the promoter from the tyrosine hydroxylase gene. Even though high levels of human alpha-synuclein accumulated in dopaminergic cell bodies, Lewy-type-positive inclusions did not develop in the nigrostriatal system. In addition, the number of nigral neurons and the levels of striatal dopamine were unchanged relative to non-transgenic littermates, in mice up to one year of age. These findings suggest that overexpression of alpha-synuclein within nigrostriatal dopaminergic neurons is not in itself sufficient to cause aggregation into Lewy body-like inclusions, nor does it trigger overt neurodegenerative changes.

Pubmed ID: 11442360 RIS Download

Mesh terms: Animals | Disease Models, Animal | Humans | Lewy Bodies | Mice | Mice, Inbred C57BL | Mice, Inbred DBA | Nerve Tissue Proteins | Parkinsonian Disorders | Phenotype | Promoter Regions, Genetic | Substantia Nigra | Synucleins | Tyrosine 3-Monooxygenase | alpha-Synuclein

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