This is a competing renewal application, seeking support to continue work with models of murine Graves' disease. Two murine models will be explored: 1) A homologous TSHR immunization model. This version of the Shimojo model uses, instead of immunization with hTSHR-transfected fibroblasts, a homologous system of cell surface-expressed mouse TSHR. 2) A transgenic approach to a Graves' disease model. This model involves the scid/scid transgenic mouse expressing human rather than murine TSHR antigen. These scid-hTSHR mice will be injected with intrathyroidal lymphocytes and engrafted with thyroid tissue from patients with Graves' disease, allowing the human TSHR-Abs to interact with the transgenic human TSHR and induce thyroid overactivity. The applicant believes that the development of both an intact mouse model for Graves' disease as well as the reproduction of the human disease in scid mice will allow a series of interventional procedures to be developed to further the understanding of autoimmune thyroid disease and will provide potential therapeutic approaches to human ATD.
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| Ban, Yoshiyuki; Concepcion, Erlinda S; Villanueva, Ronald et al. (2004) Analysis of immune regulatory genes in familial and sporadic Graves' disease. J Clin Endocrinol Metab 89:4562-8 |
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| Ando, Takao; Latif, Rauf; Davies, Terry F (2004) Concentration-dependent regulation of thyrotropin receptor function by thyroid-stimulating antibody. J Clin Invest 113:1589-95 |
| Ban, Y; Davies, T F; Greenberg, D A et al. (2004) Arginine at position 74 of the HLA-DR beta1 chain is associated with Graves' disease. Genes Immun 5:203-8 |
| Latif, R; Ando, T; Davies, T F (2004) Monomerization as a prerequisite for intramolecular cleavage and shedding of the thyrotropin receptor. Endocrinology 145:5580-8 |
| Ando, Takao; Davies, Terry F (2004) Self-recognition and the role of fetal microchimerism. Best Pract Res Clin Endocrinol Metab 18:197-211 |
| Ban, Y; Davies, T F; Greenberg, D A et al. (2003) Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease. Genes Immun 4:586-93 |
| Villanueva, R; Greenberg, D A; Davies, T F et al. (2003) Sibling recurrence risk in autoimmune thyroid disease. Thyroid 13:761-4 |
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