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Lack of nigral pathology in transgenic mice expressing human alpha-synuclein driven by the tyrosine hydroxylase promoter.
Neurobiol Dis. 2001 Jun; 8(3):535-9.ND

Abstract

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.

Authors+Show Affiliations

Dementia Research Group, Nathan Kline Institute/New York University Medical School, 140 Old Orangeburg Road, Orangeburg, New York 10962, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11442360

Citation

Matsuoka, Y, et al. "Lack of Nigral Pathology in Transgenic Mice Expressing Human Alpha-synuclein Driven By the Tyrosine Hydroxylase Promoter." Neurobiology of Disease, vol. 8, no. 3, 2001, pp. 535-9.
Matsuoka Y, Vila M, Lincoln S, et al. Lack of nigral pathology in transgenic mice expressing human alpha-synuclein driven by the tyrosine hydroxylase promoter. Neurobiol Dis. 2001;8(3):535-9.
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 alpha-synuclein driven by the tyrosine hydroxylase promoter. Neurobiology of Disease, 8(3), 535-9.
Matsuoka Y, et al. Lack of Nigral Pathology in Transgenic Mice Expressing Human Alpha-synuclein Driven By the Tyrosine Hydroxylase Promoter. Neurobiol Dis. 2001;8(3):535-9. PubMed PMID: 11442360.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lack of nigral pathology in transgenic mice expressing human alpha-synuclein driven by the tyrosine hydroxylase promoter. AU - Matsuoka,Y, AU - Vila,M, AU - Lincoln,S, AU - McCormack,A, AU - Picciano,M, AU - LaFrancois,J, AU - Yu,X, AU - Dickson,D, AU - Langston,W J, AU - McGowan,E, AU - Farrer,M, AU - Hardy,J, AU - Duff,K, AU - Przedborski,S, AU - Di Monte,D A, PY - 2001/7/10/pubmed PY - 2001/8/17/medline PY - 2001/7/10/entrez SP - 535 EP - 9 JF - Neurobiology of disease JO - Neurobiol Dis VL - 8 IS - 3 N2 - 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. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/11442360/Lack_of_nigral_pathology_in_transgenic_mice_expressing_human_alpha_synuclein_driven_by_the_tyrosine_hydroxylase_promoter_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(01)90392-4 DB - PRIME DP - Unbound Medicine ER -