Type I Diabetes (Nonobese Diabetic Mouse Model)
TID is an autoimmune disease in which the insulin-producing β cells in the pancreatic islets of Langerhans are gradually destroyed by autoreactive T cells over a period of months to years. After about 80 percent of the islet cells are destroyed, insulin deficiency and a severe form of insulin-dependent diabetes marked by ketoacidosis develops. The disease usually affects children and young adults but can occur at any age. Males and females are affected equally. The highest incidence is in Scandinavians (35 per 100,000 per year). Individuals with a genetic susceptibil-ity to the disease are thought to develop autoimmunity in response to an undefined environmental trigger. Most patients with TID produce anti-islet cell autoantibod-ies reactive with insulin, glutamic acid decarboxylase, ICA-512/IA-2, phogrin, or other antigens. These autoantibodies generally appear before the onset of clini-cal diabetes and have been used for early diagnosis of the condition.
The nonobese diabetic (NOD) mouse is the most useful model of autoimmune TID. NOD mice spontaneously develop marked infiltration of T cells into the pancreatic islets. The infiltrating T cells selectively destroy the pancreatic β cells. In addition to diabetes, NOD mice spon-taneously develop autoimmune responses involving other tissues, including sali-vary gland, lacrimal gland, thyroid gland, parathyroid gland, adrenal gland, testis, large bowel, and red blood cells. NOD mice also are susceptible to exogenously induced autoimmune diseases, such as experimental autoimmune thyroiditis, colitis-like wasting disease, encephalomy-elitis, and SLE. Defects related to several genes, including the MHC class II, CTLA-4, and IL-2, have been associated with the susceptibility to diabetes. T cells play an important role in the development and progression of disease, whereas B cells are not required at the effector stage of TID in NOD mice.