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, Dennis W Dickson, W. J. Langston, E. McGowan, M. Farrer, J. Hardy, K. Duff, S. Przedborski, D. A. Di Monte

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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 - 2001

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Synucleins
Tyrosine 3-Monooxygenase
Substantia Nigra
Transgenic Mice
Pathology
Lewy Bodies
Corpus Striatum
Somatotypes
Dopaminergic Neurons
Parkinsonian Disorders
Parkinson Disease
Dopamine
Neurons
Mutation

ASJC Scopus subject areas

  • Neurology

Cite this

Matsuoka, Y., Vila, M., Lincoln, S., McCormack, A., Picciano, M., LaFrancois, J., ... 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

Lack of nigral pathology in transgenic mice expressing human α-synuclein driven by the tyrosine hydroxylase promoter. / Matsuoka, Y.; Vila, M.; Lincoln, S.; McCormack, A.; Picciano, M.; LaFrancois, J.; Yu, X.; Dickson, Dennis W; Langston, W. J.; McGowan, E.; Farrer, M.; Hardy, J.; Duff, K.; Przedborski, S.; Di Monte, D. A.

In: Neurobiology of Disease, Vol. 8, No. 3, 2001, p. 535-539.

Research output: Contribution to journalArticle

Matsuoka, Y, Vila, M, Lincoln, S, McCormack, A, Picciano, M, LaFrancois, J, Yu, X, Dickson, DW, Langston, WJ, McGowan, E, Farrer, M, Hardy, J, Duff, K, Przedborski, S & Di Monte, DA 2001, 'Lack of nigral pathology in transgenic mice expressing human α-synuclein driven by the tyrosine hydroxylase promoter', Neurobiology of Disease, vol. 8, no. 3, pp. 535-539. https://doi.org/10.1006/nbdi.2001.0392
Matsuoka, Y. ; Vila, M. ; Lincoln, S. ; McCormack, A. ; Picciano, M. ; LaFrancois, J. ; Yu, X. ; Dickson, Dennis W ; Langston, W. J. ; McGowan, E. ; Farrer, M. ; Hardy, J. ; Duff, K. ; Przedborski, S. ; Di Monte, D. A. / Lack of nigral pathology in transgenic mice expressing human α-synuclein driven by the tyrosine hydroxylase promoter. In: Neurobiology of Disease. 2001 ; Vol. 8, No. 3. pp. 535-539.
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