Lessons from studies with genetic forms of diabetes in the mouse

Genetically defined animal models of diabetes have many advantages over models in which the genetic component has not been established. Such models permit predictable numbers of normal and afflicted animals, differing by only a single gene, to be produced at will. Maintenance of these individual mutations in inbred strains of mice permits an evaluation of any gene-host interactions that act by modifying the severity of the diabetic condition. These genetic models provide precision tools for research in which the mutant gene itself, the inbred background, and the environment can be manipulated at will. In addition there is sufficient knowledge about the arrangement of individual genes in chromosomes in the mouse to permit one to identify, and use, closely linked markers in order to predict with confidence the mice destined to become diabetic. Such studies on the preclinical stages are of utmost importance and cannot be undertaken conveniently in any other model. Our studies with genetic mouse models have established that there are at least six genes in the mouse that can cause diabetes and obesity syndromes. The severity of the diabetes produced depends on the interaction of the mutant gene with the host inbred background as well as with other environmental factors. Establishing the nature of these interactions and the possible primary lesions involved in each genetic syndrome should have major ramifications in studies dealing with human diabetes.