PANCREATIC IL-10 INDUCES DIABETES IN NOD, B6 IDD3 IDD10 MICE

Transgenic NOD backcross mice expressing pancreatic interleukin 10 (IL -10) were crossed and backcrossed to NOD.B6 Idd3 Idd10 mice, which hav e diabetes-resistance alleles at Idd3 and Idd10 on chromosome 3 and ha ve a very low frequency diabetes and insulitis. Insulitis and diabetes developed in almost all IL-10 transgenic backcross 1 (BC1) mice of th e H2g(7/g7) haplotype regardless of the allelic status at Idd3 and Idd 10. Furthermore, diabetes occurred in 23% of IL-10 transgenic H2g(7/d) BC1 mice. These results indicate that pancreatic IL-10 is able to ove rcome the diabetes protection afforded by C57BL/6 (B6)-derived alleles at Idd3 and Idd10 as well as the absence of NOD MHC homozygosity, if other non-MHC NOD-derived Idd alleles are provided.