UCSF researchers have created the first transgenic mouse to display the earliest signs of Parkinson’s disease using the genetic mutation that is known to accompany human forms of the disease.

The mouse model, which expresses the same mutant proteins as human Parkinson’s patients, also displays early signs of constipation and other gastrointestinal problems that are a common harbinger of the disease in humans.

As a result, researchers say, these animals could serve as a means of investigating therapies for reversing the neurological dysfunction of the disease at its earliest stages.

The findings are featured as the cover story in the May 1 issue of the journal Human Molecular Genetics and are available online at http://hmg.oxfordjournals.org/cgi/content/full/19/9/1633.

Researchers have long suspected that the neurological component of Parkinson’s, which causes tremors and stiffness among other symptoms, is actually a late-stage effect of a larger, systemic problem, according to UCSF geneticist Robert L. Nussbaum, MD, who was senior author on the paper.

“This new model validates that theory by mimicking what we know to be the genetic pathway leading to Parkinson’s, while also displaying the earliest symptoms that occur in humans,” said Nussbaum, who is the Holly Smith Distinguished Professor in Medicine and chief of the UCSF Division of Medical Genetics. “This will give us an important tool in identifying an early intervention for this devastating disease.”

Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s, affecting 1.5 percent of adults over 55 years of age, and is typically characterized by motor disorders such as tremors, rigidity and postural instability.

Several non-motor abnormalities also frequently accompany Parkinson’s, including depression, sleep disorders and gastrointestinal 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.

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