NOD mice develop spontaneous insulin-dependent diabetes mellitus (IDDM) associated with infiltration of pancreatic islets with mononuclear cells. Islet infiltration results in autoimmune destruction of insulin-secreting β-cells. Because in humans and BB rats diabetes is often associated with autoimmune thyroid disease (ATD), the NOD mouse model was examined for evidence of thyroiditis and serum antibodies reactive with mouse thyroid membrane antigens (MTMAs). The incidence of thyroiditis was 77% in mice > 180 days old, 67% in mice 61–180 days old, 72% in mice 31–60 days old, 74% in mice 21–30 days old, 78% in mice 11–20 days old, and 90% in mice ≤10 days old. NOD mice ≤30 days old had less-severe thyroiditis than animals > 180 days old. There was no significant different in severity of thyroiditis between any of the other age-groups tested. The incidence of thyroiditis was not increased in diabetic compared with nondiabetic animals, nor was an association found between thyroiditis and sex. The high incidence of thyroiditis in the ≤30-day-old age-group indicates that infiltration of lymphocytes into the thyroid can precede initiation of insulitis in this model. Although both thyroiditis and insulitis in NOD mice began early (by the 1st and 2nd mo of life, respectively), no significant association between infiltration of these two organs was noted in individual mice. Circulating antibodies to MTMA were demonstrated in 35% of NOD mice. Anti-MTMA antibodies were found significantly more frequently in NOD mice with thyroiditis than in those without mononuclear cell infiltration. Antibodies of this specificity precede the onset of diabetes and are likely to be secondary to mononuclear cell–mediated thyroid cell damage, although this has not been proven. The NOD mouse, in addition to being an excellent animal model for IDDM, can also be studied as a model for ATD. In addition NOD mice may be useful for exploring the underlying cause of the association between diabetes and ATD.

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