Transient insulin autoantibody expression independent of development of diabetes: Comparison of NOD and NOR strains

NOD mice spontaneously develop anti-insulin autoantibodies associated with the subsequent development of diabetes. NOD mice that express insulin autoa ntibodies at 8 weeks of age have a diabetes risk exceeding 90%, while mice that do not express autoantibodies by 16 weeks have a risk of less than 20% . NOD female mice expressed insulin autoantibodies more often than male mic e (13/15(+) vs. 6/15(+)). Autoantibodies characteristically developed betwe en 8 and 20 weeks and then for most mice became negative at diabetes onset in NOD mice. In the diabetes-free strain NOR mice, spontaneous expression o f insulin autoantibodies was observed in less mice (female 8/15(+), male 3/ 10(+)) compared to NOD mice. The expression of autoantibodies was transient in NOR mice and followed the same time-course as for NOD mice and they wer e all negative by 28 weeks (without progression to diabetes). No correlatio n was found in NOR mice between the levels of autoantibodies and insulitis. The program of insulin autoantibody expression is regulated over approxima tely 5 months for both NOD and NOR mice with only NOD mice developing diabe tes, indicating that depending upon genetic combination, the presence of in sulin autoantibodies does not always predict diabetes development. In addit ion, this data is not consistent with the hypothesis that the time-course o f autoantibodies simply reflects the destruction of beta -cells with develo pment of diabetes. (C) 2001 Academic Press.