Scientists identified a gene that may play a role in the development of type 1 diabetes. Examining genes from a mouse model of type 1 diabetes, the scientists found that cells in the animals’ pancreatic lymph nodes make two forms of the same gene called deformed epidermal autoregulatory factor 1 (Deaf1). One form of this gene encodes full-length, functional Deaf1 protein, while the other encodes a shorter, nonfunctional variant form. The research suggests that the full-length, functional form of Deaf1 may control the production of molecules needed to eliminate immune cells that can destroy insulin-producing cells in the pancreas, causing type 1 diabetes. Moreover, the presence of the Deaf1 variant was found to prevent the full-length Deaf1 protein from functioning normally. Additional experiments showed that the variant form inhibited turning on genes needed to produce certain molecules involved in immune regulation. Researchers also found that levels of the variant form of Deaf1 were higher in people with type 1 diabetes compared to levels in people without the disease. In addition, the human variant form inhibited the full-length form from functioning normally. The research suggests that the development of type 1 diabetes may in part be due to increased levels of the Deaf1 variant protein in pancreatic lymph nodes. Increased levels of Deaf1 variant may, in turn, lead to reduced production of molecules that are required to educate the immune system not to attack the body’s own cells, including the insulin-producing cells of the pancreas. Furthermore, the findings suggest that the Deaf1 variant form may predict risk for type 1 diabetes and be a target for therapy.
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Yip L, Su L, Sheng D, Chang P, Atkinson M, Czesak M, Albert PR, Collier AR, Turley SJ, Fathman CG, and Creusot RJ: Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes. Nat Immunol 10: 1026-1033, 2009.
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