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Mutant rats offer clues to medical mystery
Date:2/17/2009

HOUSTON (Feb. 17, 2009) A research project at Rice University has brought scientists to the brink of comprehending a long-standing medical mystery that may link cardiovascular disease, osteoporosis and perhaps even Alzheimer's disease.

And for that, we can thank the rat.

The recent paper in Artery Research by Rice evolutionary biologist Michael Kohn and his team reports they have found that common rats with a genetic mutation have developed a resistance to rat poison, aka warfarin. That's good news for the rats, but it comes at a price. The mutation also leaves them susceptible to arterial calcification and, potentially, osteoporosis.

The discovery is certainly good news for humans.

In the mutated gene, the researchers found what could be the link that solves the calcification paradox, the puzzling association between metabolic bone disease and vascular calcification that has eluded researchers for years. Kohn, an assistant professor of ecology and evolutionary biology, collaborated with Roger Price of the Baylor College of Medicine and Hans-Joachim Pelz of the Julius Kuehn Institute in Germany.

Kohn said a good part of the answer lies in the vitamin K cycle, which is known to regulate the coagulation of blood clotting. It's also suspected of helping keep calcium out of the body's vessels and in its bones, which has particular ramifications for postmenopausal women for whom loss of bone density is a nagging issue.

Warfarin has long served humans as a medicine called coumadin, because it interferes with the vitamin K cycle. In regulated doses, it thins the blood by reducing its ability to clot, helping prevent heart attacks, stroke and blood clots.

In bigger doses, it once excelled as rat poison; rats that ingested the poison would simply bleed to death. But a mutation in the gene Vkorc1 effectively blocks that interference.

"I have a feeling the mutation predated the introduc
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Contact: Mike Williams
mikewilliams@rice.edu
713-348-6728
Rice University
Source:Eurekalert

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