Mouse Models and the Genetics of Diabetes

In humans, both type 1 and type 2 diabetes exemplify genetically heterogeneous complex diseases in which epigenetic factors contribute to underlying genetic susceptibility. Extended human pedigrees often show inheritance of both diabetes types. A common pathophysiological denominator in both disease forms is pancreatic -cell exposure to proinflammatory cytokines. Hence, it is intuitive that systemically expressed genes regulating -cell ability to withstand chronic diabetogenic stress may represent a component of shared susceptibility to both major disease forms. In this review, the authors assemble evidence from genetic experiments using animal models developing clearly distinct diabetes syndromes to inquire whether some degree of overlap in genes contributing susceptibility can be demonstrated. The conclusion is that although overlap exists in the pathophysiological insults leading to -cell destruction in the currently studied rodent models, the genetic bases seem quite distinct. Diabetes 54 (Suppl. 2):S151–S158, 2005