Animal Models of Type 1 Diabetes Mellitus

Summary

Type 1 diabetes (T1D) or insulin-dependent diabetes is an autoimmune disease caused by the selective destruction of insulin secreting β cells in the pancreas by autoreactive CD4⁺ and CD8⁺ T lymphocytes. Animal models of the spontaneous disease as well as genetically modified models have contributed significantly to our understanding of both the pathogenesis and the pathophysiology of the disease. In particular, animal models have allowed a better approach to the complex problem of genetic and environmental factors that are important not only for disease predisposition but also for disease protection. The molecular characterization of triggering autoantigens has also been facilitated by the study of animal models. Although various molecules expressed by β cells are well-recognized targets of the autoimmune response, the use of particular genetically modified mouse models has recently pointed to proinsulin/insulin as the primary autoantigen. Last but not least, when used adequately, animal models of T1D have also been helpful in preclinical studies to search for new immunointervention strategies applicable to the clinic. The overall conclusion of >30 years of studies conducted using animal models of T1D is that they recapitulate quite satisfactorily the human situation. In analyzing the data, it is, however, essential to consider that each of the mouse or rat strains used is genetically identical. In fact, they represent multiple copies of a single individual which is of course not the case for the clinical situation.