Non-obese diabetic(NOD) mice develop an autoimmune diabetes, becoming hyperglycemic after 3 months of age. Onset diabetes animal shows destruction of insulin-secreting pancreatic beta cells associated with a lymphocytic infiltrate(insulitis) with autoantibodies to beta cells being found even before the onset of symptoms.
Several genes control IDDM in NOD mouse. A susceptibility gene(Idd-1) which strongly influence to this disease has been located in the murine MHC on chromosome 17. NOD mouse does not express 1-E owing to deletion in the promotor region of I-E alpha chain gene. And sequence of NOD I-A beta chain in the fuse external domain is unique with His 5ti and 57 Ser replacing Pro and Asp, respectively, at these position. A non-MHG gene, designated Idd-2 Ras been tentatively assigned to mouse chromosome 9. Idd-3 gene which located chromesome 3 may be essential for the development of insulitis. Idd-4 gene which may infuence the frequency of insulitis and may be to control fine progression of severe insulitis to overt diabetes.
Interesting animal model, transgenic mice were created that express introduced transegenes in the pancreatc islet cells and develop IDDM. Several investigators have construct transgenic inbred mice that express a foreign class I or class II MHC molecule. Breeding with I-E positive strains or the expression of various transgenic I-A or I-E molecules in NOD mice reduces the incidence of the disease.
Accumulating evidence strongly suggests that diabetes of NOD mouse is of an autoimmune origin. The major role of autoimmune in NOD mouse may include L3T4, Lyt-2 and macrophage. Electron microscopic studies has been shown endogenous retrovirus particle were frequently found in the beta cells.
Many trials attemped to intervence in the development of diabetes or insulitis in NOD. They include not only immunosuppressive drugs of immunological manipulations, but also other treatments of which the mechanism of action is as yet uncertain.
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