Mouse models of alpha-synucleinopathy and Lewy pathology

Sommer, B. and Barbieri, S. and Hofele, K. and Wiederhold, K. and Probst, A. and Mistl, C. and Danner, S. and Kauffmann, S. and Spooren, W. and Tolnay, M. and Bilbe, G. and Kafmann, S. and Caromi, P. and Ruegg, M. A.. (2000) Mouse models of alpha-synucleinopathy and Lewy pathology. Experimental gerontology, Vol. 35, no. 9-10. pp. 1389-1403.

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The discovery of two missense mutations (A53T and A30P) in the gene encoding the presynaptic protein alpha-synuclein (alphaSN) that are genetically linked to rare familial forms of Parkinson's disease and its accumulation in Lewy bodies and Lewy neurites has triggered several attempts to generate transgenic mice overexpressing human alphaSN. Analogous to a successful strategy for the production of transgenic animal models for Alzheimer's disease we generated mice expressing wildtype and the A53T mutant of human alphaSN in the nervous system under control of mouse Thy1 regulatory sequences. These animals develop neuronal alpha-synucleinopathy, striking features of Lewy pathology, neuronal degeneration and motor defects. Neurons in brainstem and motor neurons appeared particularly vulnerable. Motor neuron pathology included axonal damage and denervation of neuromuscular junctions, suggesting that alphaSN may interfere with a universal mechanism of synapse maintenance. Thy1-transgene expression of wildtype human alphaSN resulted in comparable pathological changes thus supporting a central role for mutant and wildtype alphaSN in familial and idiopathic forms of diseases with neuronal alpha-synucleinopathy and Lewy pathology. The mouse models provide means to address fundamental aspects of alpha-synucleinopathy and to test therapeutic strategies.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Pergamon Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:17 Apr 2019 08:21
Deposited On:22 Mar 2012 13:36

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