Mouse clue to Parkinson's disease
By Lidia Wasowicz
STANFORD, California, (UPI): Studies of mutant staggering mice are pointing to a gene that may play a role in Parkinson's disease, findings that both surprised and excited scientists, researchers said Thursday.
Reporting in the journal Nature Genetics, the Stanford University researchers said they have identified the mutant gene responsible for the unusual mice that cannot walk straight -- and found a nearly identical gene in humans.
"This finding, both surprising and exciting, opens up a whole new series of challenges for the realm of developmental neurogenetics," Dan Goldowitz of the University of Tennessee Health Sciences Center in Memphis and Richard Smeyne of Hoffmann- LaRoche in Nutley, New Jersey, wrote in an accompanying News and Views article.
The type of nerve cell lost in the disabled mice is the same as that lost in patients with Parkinson's, which strikes -- usually in old age -- one in 200 people in the United States. Therefore, the researchers speculated, studying the mice could shed light on the disabling human neurological disorder.
"This finding is guaranteed to tell us more about nervous system development," said lead study author Nila Patil of Stanford University School of Medicine in California.
The gene, also suspected in Down's syndrome, lies on chromosome 21 -- in the same region that causes Down's when the chromosome is present in three copies instead of the usual two, said co-researcher Dr. David Cox, professor of genetics.
Down's, which affects one in 10,000 people in the United States, is a leading cause of mental retardation.
The researchers had identified the mutant mouse line more than 30 years ago and have been studying the rodents ever since for insights into how the mammalian brain develops, said Richard Myers, associate professor of genetics.
The mice, dubbed "weaver" because of their swagger, have shown several other abnormalities, including sterility in the males and loss of certain nerve cells, said co-researcher Malek Faham of the University of California, San Francisco.
The newly isolated gene, when mutated, gives rise to the weaver characteristics, said co-researcher Andrew Peterson, assistant professor of genetics at Duke University in Durham, North Carolina.
"The gene's identity is something of a surprise," Patil said. "We had expected to find a gene that coded for a protein that would send signals between cells."
But what they found was that the protein Girk2 forms a pore on the outer membranes of nerve cells, controlling the outward flow of potassium ions from cells.
The researchers now are trying to figure out how the weaver mutation affects the protein's function.
"Does the mutation lead to a strangely shaped protein that functions in a new way? Or does it lead to a protein that is essentially nonfunctional?" Patil said.
"Knowing these things will help us understand the chain of chemical signals required for the development of these brain cells. There is still very little known about how neurons develop."