RESISTANCE ALLELES AT 2 NONMAJOR HISTOCOMPATIBILITY COMPLEX-LINKED INSULIN-DEPENDENT DIABETES LOCI ON CHROMOSOME-3, IDD3 AND IDD10, PROTECTNONOBESE DIABETIC MICE FROM DIABETES

Development of diabetes in NOD mice is polygenic and dependent on both major histocompatibility complex (MHC)-linked and non-MHC-linked insu lin-dependent diabetes (Idd) genes. In (F-1 x NOD) backcross analyses using the B10.H-2(g7) or B6.PL-Thy1(a) strains as the outcross partner , we previously identified several non-MHC Idd loci, including two loc ated on chromosome 3 (Idd3 and Idd10). In the current study, we report that protection from diabetes is observed in NOD congenic strains hav ing B6.PL-Thy1(a)- or B10-derived alleles at Idd3 or Idd10. It is impo rtant to note that only partial protection is provided by two doses of the resistance allele at either Idd3 or Idd10. However, nearly comple te protection from diabetes is achieved when resistance alleles are ex pressed at both loci. Development of these congenic strains has allowe d Idd3 to be localized between Glut2 and D3Mit6, close to the Il2 locu s.