The development of experimental models of autoimmune
hyperthyroid Graves' disease has proved a difficult challenge, but recently two novel methods have led to their successful development in mice. We describe our studies on replicating the adjuvant modified, human
TSH receptor (TSHR) and major histocompatibility complex class II transfected fibroblast injection system, and the plasmid
DNA vaccination method as models resembling the human disorder. The fibroblast injection model in female AKR/N (H-2k) mice led to 70% of the animals developing
thyroid-stimulating antibodies and their thyroid glands showed large
goiters with histological features of thyroid cell activation characteristic of Graves' glands. Consistent with the clinical homolog, there was no inflammatory cell infiltrate of the thyroid gland. Detailed studies on the anti-TSHR
antibodies such as thyroid-stimulating blocking antibody,
antibodies to the native TSHR by flow cytometry, and TSH-binding inhibiting Ig showed that they were heterogeneous and did not correlate with disease activity, thus resembling those present in patients with
Graves' disease. In contrast, the plasmid
DNA vaccination model in female BALB/c (H-2d) mice led to the generation of low levels of anti-TSHR
antibodies by flow cytometry, which were undetectable for
thyroid-stimulating antibodies, TSH-stimulating
blocking antibodies, and TSH-binding inhibiting Ig activity. Moreover, this model too was not accompanied by lymphocytic cell infiltration. The data demonstrate the high incidence of
hyperthyroid disease induced in the adjuvant modified, transfected fibroblast model in AKR/N mice to allow pathological mechanisms of disease to be studied.