Animal models of thyroid-associated ophthalmopathy.

Abstract

Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition most frequently associated with Graves' disease (GD). The thyrotropin receptor (TSHR) is an important target of the autoimmune response in both disorders. The last 5 years have seen some progress in the development of animal models, induced with TSHR preparations and reproducing some or all of the features of GD and TAO with variable incidence. The most promising approaches have used: (1) treatment of AKR/N mice with cells transfected with the homologous major histocompatibility complex class II molecule to the recipients and the full-length human or murine TSHR. Approximately 20% of mice develop thyroid-stimulating antibodies (TSAB) and increased thyroxine levels but no thyroiditis; (2) transfer of TSHR primed T cells to naive syngeneic recipients. Approximately 65% of BALBc mice develop thyroiditis and orbital changes similar to TAO; (3) genetic immunization of NMRI outbred mice with the full-length human TSHR. Approximately 20% of mice develop TSAB, hyperthyroidism, and orbital changes.