Recent developments in the relevance of animal models to Hashimoto's thyroiditis and Graves' disease

The study of animal models of autoimmune thyroid disease has just entered an exciting era, with major thrusts into new avenues of research. First, the HLA-DRB1 polymorphism has been shown to be a determinant of mouse thyroglobulin (mTg)-induced experimental autoimmune thyroiditis (EAT). Similar to murine class II transgene in conferring EAT susceptibility on resistant mice, the HLA-DRB1*0301 (DR3) transgene permits the induction of EAT with either mTg or human thyroglobulin (hTg). Second, Tg as a potential initiator of autoimmunity is reintroduced by the hTg induction of EAT in mice with a DR3-selected T-cell receptor (TCR) repertoire and by the appearance of anti-Tg in three spontaneous autoimmune thyroiditis models. Third, the completed mTg sequence will enable in-depth study of conserved and unique epitopes on mTg and hTg. Fourth, the importance of appropriate class II genes over other genetic and environmental factors is reemphasized by the secondary role of iodine residues in Tg immunogenicity and the flexibility of the TCR repertoire. Individual DR or DQ transgenes can now be tested without the complication of linkage disequilibrium. Finally, the induction of Graves' disease-like syndrome by immunizing mice with human thyroid-stimulating hormone receptor-transfected cells offers the possibility of establishing a Graves' disease model.