Grant Will Enable New Mouse Models of Kidney and Heart Disease Complications of Diabetes

The Mouse Models of Diabetic Complications Consortium group at Duke University Medical Center has received a five-year grant totaling more than $3.5 million from the National Institutes of Health to create new mouse models for diabetic kidney and heart disease.

"Creating these mouse models is vital to finding better treatments for and a better understanding of diabetic kidney and heart disease," said Dr. Thomas Coffman, principal investigator for the project. Stanford University and the University of North Carolina at Chapel Hill are collaborating with Duke on this project.

"There are currently no small animal or mouse models that precisely mimic human complications of diabetes," Coffman said. "Generating models of these diabetic complications in the mouse would be a powerful tool because of the genetic manipulations that are possible in mice. Having these models will allow us to expand the range of therapeutic interventions that we can test and should eventually lead us to answers about the causes of these complications."

The risk for diabetic complications in humans depends on genetic factors. Using genetic engineering techniques in mice, the expression of genes that may be linked to diabetic kidney and heart disease will be altered. By inducing diabetes in these engineered mouse lines, scientists can study the way the genes impact these disorders and they can study new approaches for preventing or treating these devastating complications. The experimental approach will take advantage of the technique of gene targeting pioneered in the laboratory of Oliver Smithies of the University of North Carolina at Chapel Hill, one of the collaborating investigators in the consortium.

Gene targeting involves introducing DNA designed to have specific inactivating mutations into mouse embryonic stem cells in tissue culture. These genetically altered stem cells are then injected into normal mouse tissue, which is introduced into pregnant mice. The "chimeric" mice that result contain both normal and mutated versions of the targeted gene. By breeding such mice, researchers can develop mice with both copies of the gene knocked out and can study what cell processes the gene controls and how drugs and other treatments affect the mice.

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Coffman, who is also chief of the nephrology division at Duke and a staff physician at the Durham Veterans Administration Medical Center, said that diabetes is a major concern in the fight against kidney disease since nearly half of the patients on dialysis are receiving the treatment because of diabetes-related complications. Once the mouse models are developed, Coffman says the new models will be made available to the scientific community, which will allow scientists to explore new therapeutics and gain a better understanding of diabetic kidney and heart disease.

Source: Duke University Medical Center