Neurobiology of Disease (Jun 2001)
Lack of Nigral Pathology in Transgenic Mice Expressing Human α-Synuclein Driven by the Tyrosine Hydroxylase Promoter
- Yasuji Matsuoka,
- Miquel Vila,
- Sarah Lincoln,
- Alison McCormack,
- Melanie Picciano,
- John LaFrancois,
- Xin Yu,
- Dennis Dickson,
- William J. Langston,
- Eileen McGowan,
- Matt Farrer,
- John Hardy,
- Karen Duff,
- Serge Przedborski,
- Donato A. Di Monte
Affiliations
- Yasuji Matsuoka
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Miquel Vila
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Sarah Lincoln
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Alison McCormack
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Melanie Picciano
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- John LaFrancois
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Xin Yu
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Dennis Dickson
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- William J. Langston
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Eileen McGowan
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Matt Farrer
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- John Hardy
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Karen Duff
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Serge Przedborski
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Donato A. Di Monte
- Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York, 10962; Department of Neurology and Pathology, Columbia University, 650 West 168th Street, New York, New York, 10032; Mayo Clinic Jacksonville, Birdsall Building, 4500 San Pablo Road, Jacksonville, Florida, 32224; The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California, 94089
- Journal volume & issue
-
Vol. 8,
no. 3
pp. 535 – 539
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.
