St. Louis, Oct. 5, 2008 Scientists report online this week in Nature that they have linked the health of specialized gut immune cells to a gene associated with Crohn's disease, an often debilitating and increasingly prevalent inflammatory bowel disorder.
The link to immune cells intrigued researchers at Washington University School of Medicine in St. Louis because they and others believe Crohn's disease is caused by misdirected immune responses in the intestine that damage gut tissue. In addition, cells in the mouse model scientists used for the study had altered genetic activity that could lead to increased production of certain hormones. Those same hormones are elevated in some Crohn's patients.
"We now have a significant new piece of the puzzle that is Crohn's disease, but not the solution just yet," says senior author Herbert W. "Skip" Virgin, M.D., Ph.D., the Edward Mallinckrodt Professor and head of the Department of Pathology and Immunology. "As many as 30 different areas in human DNA have potential links to Crohn's disease, and to develop new treatments it's going to be essential to find out how each of them, as well as environmental factors, contribute to the disorder."
Crohn's disease is one of the most common inherited bowel disorders. In 2002, epidemiologists estimated that it affected 400,000 to 600,000 patients in North America. Symptoms include diarrhea, abdominal pain, vomiting and weight loss. The condition can lead to partial or full intestinal blockages, which can require surgical treatment.
Research previously revealed that some Crohn's disease patients have a mutation in a gene known as Atg16L1. The mutation increases risk but doesn't automatically lead to Crohn's disease. To learn more, Ken Cadwell, Ph.D., a postdoctoral student in Virgin's lab, created and studied two lines of mice with a genetic alteration that reduced their ability to make the Atg16L1 protein.
Cadwell and his colleag
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Washington University School of Medicine