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Protection of Nonobese Diabetic Mice from Diabetes by Gene(s) Closely Linked to IFN- Receptor Loci¹

Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110

Nonobese diabetic (NOD) mice carrying a segment of chromosome flanking the disrupted IFN- receptor gene from original 129 ES cells are resistant to development of diabetes. However, extended backcrossing of this mouse line to the NOD mouse resulted in a segregation of the IFN-R-deficient genotype from the diabetes-resistant phenotype. These results indicate that the protection of NOD mice from the development of diabetes is not directly linked to the defective IFN- receptor gene but, rather, is influenced by the presence of a diabetes-resistant gene(s) closely linked to the IFN-R loci derived from the 129 mouse strain.