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UCSF transgenic mouse mimics Parkinson's earliest symptoms
Date:5/3/2010

strointestinal dysfunction, the researchers explained. Gastrointestinal dysfunction is a particularly common symptom, seen in 80 to 90 percent of patients, and often precedes the motor-control symptoms by 10 to 15 years.

The UCSF mouse model is the first to display the full gastrointestinal symptoms as well, and is consistent with the progression of the disease in humans.

Nussbaum, in collaboration with former colleague Mihael Polymeropoulos, MD, had previously identified the first Mendelian-inherited form of Parkinson's, which involves a mutation in the gene that produces alpha-synuclein proteins. Since then, he has been studying the rare, inherited forms of the disease to better understand the pathways and processes that may be involved in the more common, sporadic forms, and to create mouse models of the disease that can help in developing therapies.

The current model, based on that research, is significant in having the same genetic mutation that causes alpha-synuclein to misfold in an inherited form of Parkinson's, causing the proteins to stick together to form insoluble fibrils in the nerve cells. Those clumps, known as Lewy bodies, are often associated with Parkinson's, as well as with some other forms of dementia and multiple system atrophy.

Previous mouse models of the disease had relied on an over-expression of alpha-synuclein caused by a combination of human and mouse genes, according to the paper. The UCSF team created two new lines that only express the human form of the protein, with each line expressing one of two mutant forms that occur in human Parkinson's patients, according to lead author Yien-Ming Kuo, PhD, in the UCSF Institute for Human Genetics.

In these lines, gastrointestinal dysfunction could be seen at three months of age, reached its highest severity at six months and persisted until 18 months, which follows the human course of the disease in sporadic Parkinson's, according to the paper. That
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Contact: Kristen Bole
kbole@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

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