PANCREATIC EXPRESSION OF ANTIGENS FOR ISLET-CELL ANTIBODIES IN NONOBESE DIABETIC MICE

Diabetes-prone NOD mice of both sexes and at different ages were compared to control mice with regard to the level of pancreatic expression of certain autoantigens: antigens for islet cell antibodies (ICA antigens) and glutamic acid decarboxylase (GAD) 67 kDa. ICA antigens were compared by immunofluorescence using serial dilutions of ICA positive human sera so that differences of fluorescence intensity were due only to differences in amounts of antigen. Pancreatic GAD67 mRNAs were compared by polymerase chain reaction followed by Southern hybridization with P-32-probes and densitometry of autoradiographic bands. GAD67 product and gamma-aminobutyric acid (GABA) were compared by immunoperoxydase staining. As compared to BALB/c, C57BL6, Swiss, or F-1 mice, NOD mice displayed higher ICA antigen levels (P<0.01) both before and after insulitis onset (at 7 days, 15 days, 1 month, 2 months). ICA antigens were scarcely detectable by the first day of life, and increased with age from 7 days to 2 months (P<0.01; n=10 for each strain and at each age). Both before and after insulitis onset (4 days, 7 days, 15 days, 1 month, 2 months), amounts of GAD67 mRNAs were higher (P<0.01) in NOD mice than in BALB/c mice (n=8 for each age in each strain). This was already noted in foetuses on Day 18 of gestation (n=8). After birth, amounts of GAD67 mRNAs increased up to 1 month (P<0.04) and then decreased in older mice. The staining intensity of pancreatic sections with antisera against either GAD67 or GABA was higher (P<0.04) in islets from NOD mice than in those from control mice. Whatever the age, no significant difference was noted between female and male NOD mice with regard to ICA antigens or GAD67. The expression of ICA antigens and GAD67 was intermediate in NOD x BALB/c F-1 mice when compared to parental strains.