A Single Recessive Non-MHC Diabetogenic Gene Determines the Development of Insulitis in NOD Mice

Abstract

Insulin-dependent diabetes of man, the BB rat and the NOD mouse appears to result from autoimmune β cell destruction in a setting of genetic predisposition. The NOD mouse develops insulin-dependent diabetes secondary to islet β cell destruction by infiltrating lymphoid cells (insulitis), resulting in lack of intrinsic insulin secretion, hyperglycemia, loss of body weight and ketosis as seen in human insulin-dependent diabetes (Makino S, et al. 1980). Insulitis appears as early as 5 weeks of age. The lymphoid cells invade islets and are often seen adjacent to the ducts and blood vessels (Figure 1). The inceidence of insulitis is 90% in NOD females and 70% in NOD males at 9 weeks of age. The incidence and degree of insulitis increase with age. The NOD mouse develops diabetes usually by 6 months of age. The cumulative incidence of diabetes in our NOD/ShiJos colony is 80% in NOD females and less than 20% in NOD males at 7 months of age. In some other colonies, the incidence of diabetes in males is higher (approximately 50%) than that in our NOD/ShiJos colony (Prochazka M, et al. 1987). This could be due to differences in diets, environments and NOD-lines.