Navigation Links
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 introduction of warfarin," said Kohn. "But it was rare, because it causes side effects. It's not an advantageous mutation unless it's exposed to warfarin."

Poisoning rats without the mutation killed them, while those with the mutation multiplied. "And these rats, in the absence of poison, suffer from cardiovascular disease -- just like we do," said Kohn, adding that the kidneys of rats in the study were "calcified to an extent that is shocking."

His hope is that the equivalent gene in humans turns out to be the key to a number of ills.

"As you look at humans, this calcification of arteries is, I suspect, a very important precondition to thrombosis and stroke. So to find such a strong effect was shocking to us. We had a tough time publishing the paper because people might have thought it was too good to be true, that you can explain the effect to such a degree by looking at just one gene."

Kohn and his colleagues have begun a study on osteoporosis in rats that have the mutation, and early results are promising. "The prediction is the mutant rats have a lower bone density. And I think if we complete and confirm that as well, it would be a major breakthrough. That means one gene, one mutation, explains the so-called calcification paradox."

Finally, he noted, Alzheimer's patients tend to be vitamin K-deficient, which opens up avenues for further study. "Could there be one mutation that explains osteoporosis, arteriosclerosis and Alzheimer's? That would be huge," said Kohn.

"I think the pathway of the vitamin K cycle is underrated in terms of its importance to some of these diseases. Gas6 is a vitamin K protein expressed in the brain, and there are many more vitamin K-dependent proteins we don't know about. The question is, if the recycling capability of the vitamin-K cycle is reduced, how many of these proteins can't do what they're supposed to do?

"I think we have some surprises in store."

Kohn said it's gratifying to know that evolutionary biology can help pave the path to personalized medicine. He credits the now-published findings with helping him land a recent grant of $900,000 from the National Institute of Heart Lung Blood disease at the National Institutes of Health. Kohn will now use mutant and normal rats to find additional genes that respond to warfarin, with two purposes: first, to see if rats have recruited additional genes to battle poisons that are more potent, and second, to attain the ultimate goal of fine-tuning doses of coumadin for humans.


'/>"/>

Contact: Mike Williams
mikewilliams@rice.edu
713-348-6728
Rice University
Source:Eurekalert

Related medicine news :

1. What is the more suitable for early detection of low abundant lamivudine-resistant mutants?
2. FSU researchers mutant proteins could lead to new treatment for heart disease
3. Mutant gene causes epilepsy, intellectual disability in women
4. Effect of mutant p53 stability on tumorigenesis and drug design
5. Intrabody can mop up mutant protein in Huntingtons disease model
6. Mutant Mouse Gene Offers Clues to Hearing Loss
7. Mutant proteins result in infectious prion disease in mice
8. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
9. Health care incentive model offers collaborative approach
10. Eye-staining technique offers early detection for dry eye syndrome
11. Governor Rendell Offers adultBasic Coverage to 35,000 Uninsured Pennsylvanians
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... Oakland, CA (PRWEB) , ... March 24, 2017 ... ... present on two panels at the Advanced ERISA Benefit Claims Litigation seminar in ... and Creating the Administrative Record, The majority of cases litigated under ERISA involve ...
(Date:3/24/2017)... , ... March 24, 2017 , ... ... first Certified Medical Reiki™ Master in Frederick, MD. Judy says, “I am passionate ... during what is often a very difficult and challenging time.” , A Certified ...
(Date:3/24/2017)... ... March 24, 2017 , ... “The Adventures of Joey, The Dog Who Barks ... lives his life to the fullest, as God intended. “The Adventures of Joey, The ... mother and grandmother pursuing her passion for writing, especially about truth and human behavior. ...
(Date:3/23/2017)... ... March 23, 2017 , ... Texas Physical Therapy Specialists (TexPTS) ... Gruene Road in Building 2. The clinic is the group’s second in New Braunfels ... opening the company’s second New Braunfels location brings things full circle for the group, ...
(Date:3/23/2017)... ... March 23, 2017 , ... Dilger-Maxwell ... of the Norwalk and Vermillion areas, celebrates the newest charity campaign in ... nonprofit, community-based substance abuse prevention and peer recovery support organization providing vital ...
Breaking Medicine News(10 mins):
(Date:3/23/2017)... HICKORY, N.C. , March 23, 2017  Transportation ... accolades as an end-to-end supply chain management firm with ... of Consumer Product Solutions Rick Zaffarano was ... Star of the Supply Chain by the only publication ... the global food supply chain. "Rick has ...
(Date:3/23/2017)... 2017 Summary ... pipeline guide Primary Hyperoxaluria - Pipeline Review, H1 ... (Genito Urinary System And Sex Hormones) pipeline landscape. ... by recurrent kidney and bladder stones. It results ... Symptoms include blood in the urine, pain when ...
(Date:3/23/2017)... 23, 2017 Research and Markets has announced ... report to their offering. ... The global oxygen therapy devices market to grow ... The report, Global Oxygen Therapy Devices Market 2017-2021, has been ... experts. The report covers the market landscape and its growth prospects ...
Breaking Medicine Technology: