Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK045011-09
Application #
6380720
Study Section
Endocrinology Study Section (END)
Program Officer
Akolkar, Beena
Project Start
1993-01-01
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
9
Fiscal Year
2001
Total Cost
$284,479
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Ando, Takao; Davies, Terry F (2005) Monoclonal antibodies to the thyrotropin receptor. Clin Dev Immunol 12:137-43
Levin, Lara; Ban, Yoshiyuki; Concepcion, Erlinda et al. (2004) Analysis of HLA genes in families with autoimmune diabetes and thyroiditis. Hum Immunol 65:640-7
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
Ando, Takao; Latif, Rauf; Daniel, Samira et al. (2004) Dissecting linear and conformational epitopes on the native thyrotropin receptor. Endocrinology 145:5185-93
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
Ciullo, I; Latif, R; Graves, P et al. (2003) Functional assessment of the thyrotropin receptor-beta subunit. Endocrinology 144:3176-81
Ando, Takao; Davies, Terry F (2003) Clinical Review 160: Postpartum autoimmune thyroid disease: the potential role of fetal microchimerism. J Clin Endocrinol Metab 88:2965-71

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