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

Y. Matsuoka, M. Vila, S. Lincoln, A. McCormack, M. Picciano, J. LaFrancois, X. Yu, D. Dickson, W. J. Langston, E. McGowan, M. Farrer, J. Hardy, K. Duff, S. Przedborski, D. A. Di Monte

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221 Scopus citations

Abstract

α-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 α-synuclein have been found to be responsible for rare familial cases of Parkinsonism. To test whether overexpression of human α-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 α-synuclein protein was driven by the promoter from the tyrosine hydroxylase gene. Even though high levels of human α-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 α-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.

Original languageEnglish (US)
Pages (from-to)535-539
Number of pages5
JournalNeurobiology of Disease
Volume8
Issue number3
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Neurology

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    Matsuoka, Y., Vila, M., Lincoln, S., McCormack, A., Picciano, M., LaFrancois, J., Yu, X., Dickson, D., Langston, W. J., McGowan, E., Farrer, M., Hardy, J., Duff, K., Przedborski, S., & Di Monte, D. A. (2001). Lack of nigral pathology in transgenic mice expressing human α-synuclein driven by the tyrosine hydroxylase promoter. Neurobiology of Disease, 8(3), 535-539. https://doi.org/10.1006/nbdi.2001.0392