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 dysfunction occurred before there was any evidence of loss of smell and also before any evidence arose of pathological changes in the brain stem.

"This suggests that, at least in mice with the human proteins, these gastrointestinal symptoms are an intrinsic defect caused by the mutant protein, rather than being caused by abnormalities in brain function," Kuo said. "That knowledge could eventually help us test for the disease long before it starts to cause neurodegenerative problems and prevent them from occurring."

Source: University of California - San Francisco