Lack of Nigral Pathology in Transgenic Mice Expressing Human α-Synuclein Driven by the Tyrosine Hydroxylase Promoter
| Autor: | John LaFrancois, Alison L. McCormack, Melanie Picciano, Yasuji Matsuoka, Karen Duff, Serge Przedborski, Eileen McGowan, John Hardy, Sarah Lincoln, Miquel Vila, Xin Yu, Dennis W. Dickson, Donato A. Di Monte, William J. Langston, Matthew J. Farrer |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Tyrosine 3-Monooxygenase animal diseases Synucleins Nerve Tissue Proteins Substantia nigra Biology lcsh:RC321-571 Mice chemistry.chemical_compound Parkinsonian Disorders Dopaminergic Cell Internal medicine medicine Animals Humans Promoter Regions Genetic lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Alpha-synuclein Lewy body Tyrosine hydroxylase Parkinsonism Dopaminergic medicine.disease nervous system diseases Mice Inbred C57BL Substantia Nigra Disease Models Animal Phenotype Endocrinology Neurology chemistry nervous system Mice Inbred DBA alpha-Synuclein Lewy Bodies |
| Zdroj: | Neurobiology of Disease, Vol 8, Iss 3, Pp 535-539 (2001) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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