Transgenic mice for the study of diabetes mellitus

Several recent studies have utilized transgenic technology to explore basic questions in the pathophysiology of diabetes mellitus. The ultimate expression of altered glucose homeostasis is a theme common to them. The experimental models have been diverse, however, and, in some instances, resulted in unexpected biologic effects. Many of the studies have examined the autoimmune etiology of insulin-dependent diabetes mellitus by expressing regulatory molecules of the immune system as transgenes in islet beta cells. The molecules have included products of the major histocompatibility complex (MHC), cytokines, and other cell surface antigens. Ectopic expression of these transgenes resulted in altered immune responses directed against islets, and these transgenic mice now serve as important models to study mechanisms of immunologic tolerance. Transgenic technology is also being used to explore basic aspects of islet beta-cell physiology and insulin metabolism. beta-cell function is disrupted by transgenic beta-cell expression of molecules such as calmodulin and H-ras. Hyperexpression of insulin as a transgene can result in a syndrome resembling features of non-insulin-dependent diabetes.