TEMPORAL DISCONTINUITIES IN PROGRESSION OF NOD AUTOIMMUNE DIABETES

Consideration of the pathophysiology of insulin-dependent diabetes mel litus in the nonobese diabetic (NOD) mouse can be viewed from a tempor al perspective. We argue that there are discontinuous phases and each phase may reflect a phenotype educed by a particular set of genetic an d epigenetic events. Therefore, temporal dissection may be a useful pl atform for causal dissection and we have set out this article as follo ws: 1. Introduction. 2. ''Pre-time.'' a. Genetics. b. Parental effects . 3. Development of insulitis, a. Development of autoimmunity vs wanin g of or failure to establish tolerance.b. Importance of beta cell mass . c. Homing. 4. Onset of beta cell destruction. 5. Further Discussion.