ABSTRACT
The inbred mouse has remained the premiere organism for analyzing the genetic basis for susceptibility/resistance to spontaneous or induced diseases of biomedical significance. However, until the appearance of spontaneous, T cell–mediated insulin-dependent diabetes mellitus (IDDM) in the Nonobese Diabetic (NOD) mouse strain, diabetes investigators seeking to utilize mouse models of IDDM were limited to the analysis of experimentally induced hyperglycemia. A preliminary genetic comparison of alloxan-induced diabetes-susceptible mice (ALS) and resistant mice (ALR) strains in Japan has been reported using "classical" screening methods. NOD mice are susceptible to a variety of experimentally induced disease syndromes, including chemically induced diabetes, lupus, colitis, encephalomyelitis, and thyroiditis. Autoantibodies appear to play a secondary role in IDDM pathogenesis in NOD mice. Yet the NOD-characteristic T-lymphoaccumulation results from polygenically controlled immunodeficiencies as profound as those produced solely by the Lyp gene in BB-DP rats. Natural killer (NK) cells in NOD mice express the NK1.2 allotype and are detectable using a pan-NK monoclonal antibody.
