Glycosuria and insulitis in NOD mice expressing the HLA-DQw6 molecule

To investigate HLA-linked genes controlling the susceptibility and resistance to insulin dependent diabetes mellitus (IDDM), HLA-DQ alleles of 45 Japanese patients with IDDM were analysed, using sequence specific oligonucleotide (SSO). DQA1*0301 and DQB1*04 were positively associated (R.R = 6.6, Pc less than 0.05 and R.R. = 4.7 Pc less than 0.01) and DQA1*0103 and DQB1*0104 were negatively associated (R.R. = 0.2, Pc less than 0.01) with IDDM. DQA1*0103 and DQB1*0104 were in strong linkage disequilibrium to encode for DQw6 molecule. Therefore, in a Japanese population, the DQw6 molecule seems to control the resistance to IDDM. To determine whether or not the DQw6 molecule itself can protect against glycosuria and insulitis in NOD mice, these animals were mated with HLA-DQw6 transgenic-C57BL/6 mice (DQw6-B6) and the F1 progeny expressing the DQw6 molecule were backcrossed with NOD mice. Eighty-five female backcross progenies were classified into four groups, according to the MHC classII phenotype; I-ANOD/I-ANOD DQw6(-), I-ANOD/I-ANOD DQw6(+), I-ANOD/I-Ab DQw6(-) and I-ANOD/I-Ab DQw6(+). At the age of 16 weeks, 9.1% of the DQw6(-) I-Ab(-) mice had a glycosuria whereas none of the DQw6(+) I-Ab(-) mice had a glycosuria. At the age of 30 weeks 13.6% of the DQw6(-) I-Ab(-) mice had a glycosuria and 7.7% of the DQw6(+) I-Ab(-) mice had a glycosuria. Histological examinations of the pancreas were performed in the 30 week old mice or after the development of glycosuria.(ABSTRACT TRUNCATED AT 250 WORDS)