RESEARCH: Presenting: A Not-Quite-Parkinson's Mouse Model

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Presenting: A Not-Quite-Parkinson's Mouse Model

20 May 2002. A transgenic mouse overexpressing a mutant human form of

a-synuclein develops Lewy body inclusions that cause neurodegeneration and a

severe movement disorder, according to report in yesterday's Neuron.

A-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 a-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, Trojanowski, and colleagues at the University of

Pennsylvania in Philadelphia inserted the gene for human A53T a-synuclein

into the genome of normal mice. The mice expressing the mutant gene, but not

those expressing wild-type human a-synuclein, developed a severe

a-synucleinopathy. Among its features are a severe, complex motor impairment

leading to paralysis and death, paralleled by age-dependent intraneuronal

a-inclusions. These fibrillar lesions resemble the Lewy bodies found in

human disease. -Hakon Heimer

Reference: Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM-Y.

Neuronal a-synucleinopathy with severe movement disorder in mice expressing

A53T human a-synuclein. Neuron. 16 May 2002;34:521-33.