Many of us carry genes for diseases that we will never get. Take Crohn's disease, an autoimmune disease that attacks the digestive system: Well over half of the population holds at least a genetic variant linked to Crohn's disease, but only a fraction of them presently there . Scientists have long known that environmental triggers contribute to explain this discrepancy, but they do not know exactly how. Now, an incidental finding in mice shows that when animals with particular Crohn gene are exposed to a specific virus, they develop characteristics similar to those of individuals with time of scientific disease first noted that genes and environmental intersected in this manner in Crohn's disease. Scientists hope the finding is just the beginning of many that will show how genes and the environment combine specifically to produce all kinds of chronic diseases.
The conclusion was a fluke. Thaddeus Stappenbeck immunologist and virologist Herbert School of Medicine in St. Louis Virgin University of Washington were moving their mouse colony for a superclean facility to keep animals free of viruses that often plague laboratory mice. The duo and his colleagues worked with mice carrying a gene called ATG16L1 , which increases the risk of Crohn's disease in people. When the mice were moved, they showed more abnormalities in their intestinal cells. "There must be an environmental trigger present in a system, but not the other," Virgin said he thought at the time.
The researchers immediately hosted on suspects: a virus that Virgin was discovered and reported in Nature ago 7 years called murine norovirus. Noroviruses are common among people, too, for which they cause gastrointestinal disorders. One of the most famous is the Norwalk virus, which often sickens people in close quarters, such as on cruise ships. For years, gastroenterologists have noticed that patients who come to them with newly diagnosed Crohn's disease often have suffered some kind of stomach virus recently.
To test whether murine norovirus, which was not present in the plant "clean" might explain the difference in their mice, the researchers infected mice ATG16L1 with particular strain of murine norovirus, named MNV CR6. After 7 days, the inflammation showed a type of intestinal cell called the most germs home loaded cells Paneth the same abnormalities the mice had done in their earlier ,. Inflammation is very similar to what is observed in patients with Crohn's disease in these same cells. Another strain of norovirus has not had this, and mice ATG16L1 remained healthy.
Scientists have long believed that, in addition to genetic and viral exposure, Crohn's disease is driven in part by an abnormal balance of bacteria in the gut. Virgin, Stappenbeck and colleagues estimated taking ATG16L1 mice that had been exposed to norovirus they were destined to suffer bowel problems and fed them a solution that hurts the intestines further. In healthy mice, the solution induced ulcers, was expected. In affected mice, injection led to even more features resembling Crohn's disease, including inflammation through the colon wall, reports the team in issue tomorrow Cell .
R. Balfour Sartor, a gastroenterologist at the University of North Carolina, Chapel Hill, and Senior Medical Advisor for Crohn's and Colitis Foundation of America in New York, says the work could help to explain why the majority of people who have Crohn's genes don 't develop the disease. It shows that many factors are required to induce Crohn's disease, he said, but not one sufficient to itself.
However, much work remains to be done to determine how to apply the results to people, said Sartor. He also whether other viruses in the presence of ATG16L1 , may have the same effects, and whether other genes combined with Crohn this norovirus do, too.
Stappenbeck said that another great mystery how exactly is the mechanism that norovirus is combined with this particular gene to produce abnormalities in the intestine. He and Virgin also plans to start looking at the human suffering of Crohn's disease virus to see what they were exposed to.
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