A transgenic mouse overexpressing a mutant human form of α-synuclein develops Lewy body inclusions that cause neurodegeneration and a severe movement disorder, according to report in yesterday's Neuron.
α-synuclein is a major component of Lewy bodies, the intraneuronal inclusions found in Parkinson's disease, in the Lewy body variant of Alzheimer's disease, and a number of other neurodegenerative diseases. Since the discovery that the human α-synuclein variant A53T was found in a number of families with inherited Parkinson's, there has been a focus on investigating whether an overabundance of this mutant form leads to Lewy bodies and neuropathology.
Virginia Lee, John Trojanowski, and colleagues at the University of Pennsylvania in Philadelphia inserted the gene for human A53T α-synuclein into the genome of normal mice. The mice expressing the mutant gene, but not those expressing wild-type human α-synuclein, developed a severe α-synucleinopathy. Among its features are a severe, complex motor impairment leading to paralysis and death, paralleled by age-dependent intraneuronal α-inclusions. These fibrillar lesions resemble the Lewy bodies found in human disease.—Hakon Heimer
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- Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron. 2002 May 16;34(4):521-33. PubMed.