Comparison of High— and Low—Diabetes-Incidence NOD Mouse Strains

The nonobese diabetic (NOD) mouse is a model of insulin-dependent diabetes mellitus. These mice develop insulinopenia and hyperglycemia secondary to α-cell destruction, which is associated with insulitis and autoantibody production. We have two strains of NOD mice: a low-incidence strain (NOD/Wehi), in which <10% females and <1% males develop diabetes by 150 days despite intense insulitis, and a highincidence strain (NOD/Lt), in which most females and many males develop diabetes by 150 days. This phenotypic difference has been maintained for 24 mo despite identical housing in our specific pathogenfree unit. Reciprocal skin grafting and allozyme electrophoresis have not identified a difference between the strains. Mixed-lymphocyte cultures were performed with splenic T-lymphocytes cultured with equal numbers of irradiated stimulator splenocytes for 3–6 days. NOD/Wehi mice demonstrated a heightened syngeneic mixed-lymphocyte response (SMLR), averaging 19% of the allogeneic response to CBA/CaHWehi cells. The response to NOD/Lt stimulator cells was not significantly different from the syngeneic response. In contrast, NOD/Lt mice had an SMLR similar to that of BALB/cAnBradleyWehi control mice, averaging 5% of the allogeneic response. NOD/Lt cells also responded similarly to NOD/Wehi stimulator cells and briskly to allogeneic cells. The heightened SMLR in NOD/Wehi mice may reflect active generation of suppressor function, and this may account for the low incidence of diabetes.