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Gewählte Publikation:

Rockenstein, E; Mallory, M; Hashimoto, M; Song, D; Shults, CW; Lang, I; Masliah, E.
Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters.
J NEUROSCI RES. 2002; 68(5): 568-578.
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Abstract:
Accumulation of alpha-synuclein has been associated with neurodegenerative disorders, such as Lewy body disease and multiple system atrophy. We previously showed that expression of wild-type human alpha-synuclein in transgenic mice results in motor and dopaminergic deficits associated with inclusion formation. To determine whether different levels of human alpha-synuclein expression from distinct promoters might result in neuropathology mimicking other synucleopathies, we compared patterns of human alpha-synuclein accumulation in the brains of transgenic mice expressing this molecule from the murine Thy-1 and platelet-derived growth factor (PDGF) promoters. In murine Thy-1-human alpha-synuclein transgenic mice, this protein accumulated in synapses and neurons throughout the brain, including the thalamus, basal ganglia, substantia nigra, and brainstem. Expression of human alpha-synuclein from the PDGF promoter resulted in accumulation in synapses of the neocortex, limbic system, and olfactory regions as well as formation of inclusion bodies in neurons in deeper layers of the neocortex. Furthermore, one of the intermediate expressor lines (line M) displayed human alpha-synuclein expression in glial cells mimicking some features of multiple system atrophy. These results show a more widespread accumulation of human alpha-synuclein in transgenic mouse brains. Taken together, these studies support the contention that human alpha-synuclein expression in transgenic mice might mimic some neuropathological alterations observed in Lewy body disease and other synucleopathies, such as multiple system atrophy.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Antigens, Thy-1 - genetics
Gene Expression - genetics
Humans - genetics
Lewy Body Disease - pathology
Limbic System - pathology
Mice - pathology
Mice, Transgenic - pathology
Multiple System Atrophy - pathology
Neocortex - pathology
Nerve Tissue Proteins - genetics
Neuroglia - metabolism
Neurons - metabolism
Platelet-Derived Growth Factor - genetics
Promoter Regions (Genetics) - genetics
Substantia Nigra - pathology
Synucleins - pathology
alpha-Synuclein - pathology

Find related publications in this database (Keywords)
alpha-synuclein
Lewy body disease
LBD
multiple system atrophy
MSA
transgenic mice
Thy-1
platelet-derived growth factor (beta chain)
PDGF-beta
promoter
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