Accidentally-bred mice may hold the cure for a debilitating intestinal disease.
The mice, originally bred by a group of Japanese scientists to study the aging process, developed lower intestinal problems and now are key players in the study of Crohn's disease, which is the inflammation of the lower intestine.
After scientists realized the mice were no good for their study, they shipped them all the way to Charlottesville, where University researchers are studying the disease.
The University research got a jump start recently when the National Institute of Diabetes and Digestive and Kidney Diseases gave a $5.1 million grant over five years to fund further study of Crohn's disease.
"If this mouse model truly represents human disease, this research will lead to a mechanistic understanding of Crohn's disease and help in the development of new therapeutic strategies," said Biomedical Engineering Prof. Klaus F. Ley.
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Although it is not a fatal disorder, it greatly "compromises quality of life" for those affected by it, said Fabio Cominelli, director of the Digestive Health Research Center.
The grant is divided into four projects. Cominelli will supervise how the grant is allocated, as well as one of the projects.
He said his specific project involves studying the role of certain molecules called cytokines in the development of Crohn's disease. Cytokines are proteins that are secreted by white blood cells and used to communicate with other white blood cells. They "are important in mediating the disease," Cominelli said, and trying to block these molecules could lead to new treatments for the disease.
The remaining three projects will be overseen by Marcia McDuffie, associate professor of microbiology and internal medicine, Steven M. Cohn, associate professor of internal medicine and Ley, professor of biomedical engineering.
McDuffie said her project involves finding the genes that make people susceptible to Crohn's diseae, which is often difficult to diagnose. Identifying the genes involved in the development of the disease could lead to faster methods of diagnosis. Crohn's disease, unlike other genetic diseases such as cystic fibrosis, is not caused by a mutation in a single gene. It is more like cancer - multiple defective genes are involved.
"Crohn's disease seems to be produced by the interaction of many genes," McDuffie said.
McDuffie said they have already identified two particular regions of the mouse chromosomes thought to be involved in the development of disease.
Ley's study focuses on the role of white blood cells in the disease. He specifically studies molecules that adhere to white blood cells and recruit them into inflamed tissue. He said that these molecules are "absolutely required for [this] disease," and the goal of his project will be to identify those that are specifically involved in Crohn's disease. The recruitment of the white blood cells is responsible for many disease symptoms.
The importance of these molecules identifies them as possible targets for new Crohn's disease treatments, Ley said, although such questions have not been explored yet.
He will also test his theories using the mouse model for the disease.
Crohn's disease is diagnosed using a combination of clinical evaluations and tests such as endoscopy, Cominelli said. Cominelli also said that treatment involves trying to alleviate the symptoms. There is no cure for this disease, and this has become an important focus for the team of researchers.
"Our goal is to attempt to provide a cure for a group of these patients in the next five to 10 years," Cominelli said.
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