$15 Million Grant Marries Bioinformatics with Mouse Models

An MCG bioinformatics expert is coordinating a national effort to develop animal models to study diabetes complications.

Dr. Richard A. McIndoe, associate director of the MCG Center for Biotechnology and Genomic Medicine, has received a $15 million, fiveyear grant—MCG’s largest ever—to continue operating the Coordinating and Bioinformatics Unit for the innovative National Institutes of Health project, Animal Models of Diabetic Complications Consortium.

He also will begin providing the same services for the Mouse Metabolic Phenotyping Centers, another NIHfunded consortium of centers offering mousetesting expertise to scientists nationwide for diseases including diabetes, obesity and related disorders.

“The NIH recognized years ago that there were few good animal models that mimic the complications of diabetes,” Dr. McIndoe said. Even the NOD mouse, a spontaneous model for type 1 diabetes, is inadequate, primarily because complications tend to come with age and mice have a relatively short lifespan.

Diabetes complications include cardiovascular and kidney disease, diabetic retinopathy and nerve and bladder damage. “Diabetic cardiovascular disease is probably the biggest mortality risk for type 1 and 2 diabetes; somewhere around 60 to 70 percent of diabetic mortality can be associated with cardiovascular disease,” Dr. McIndoe said.

The high risk of model development impeded financial support until the NIH committed funds several years ago. Scientists who receive funding agree to make their development data and resulting animal models available to the scientific community.

In 2001, while on the University of Florida faculty, Dr. McIndoe received the first grant to provide administrative and coordinating activities for investigators working on model development. Work includes organizing semiannual Executive Steering Committee meetings, monthly teleconferences, workshops, training sessions and organizing activities for the External Advisory Boards.

A major task was developing a computer system that could store and analyze the huge amount of data generated by investigators, then share it with scientists all over the world through a Web portal, www.amdcc.org.

To date, about 70 animal models have been studied, information on about 25 has been deposited in the database Dr. McIndoe developed, and about 20 of those models will soon be available from mouse repositories. Scientists will generally need several models to mimic human disease. “They don’t want an animal model that looks like a mouse problem; they want an animal model that looks like a human problem,” Dr. McIndoe said.

For the second round of NIH funding, each investigator will propose two new models and turn them over to a husbandry core for development. “Once created, the models will be sent back to the investigators, who will be in charge of understanding the pathology of the complications,” said Dr. McIndoe. The NIH integrated operation of the consortium with the Mouse Metabolic Phenotyping Centers, which also were up for grant renewal. Th