Temporal discontinuities in progression of NOD autoimmune diabetes.

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