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

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


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


Neurobiology of disease

Publication Data

June 9, 2001

Associated Grants

  • Agency: NIEHS NIH HHS, Id: ES10442

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