| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Department of Pediatrics (S.K., N.S., K.Y., Ak.H., Y.K., H.N.) and Second Department of Internal Medicine (Ai.H., Y.S., K.T.), Chiba University School of Medicine, Chiba 260, Japan; SRL, Inc. (Y.W.), Hachioji 192, Japan; Cell Regulation Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (L.D.K.), Bethesda, Maryland 20892; and Department of Molecular Biology, Tokyo Metropolitan Institute of Gerontology (N.M.), Tokyo 173, Japan
Address all correspondence and requests for reprints to: Dr. Naoki Shimojo, Department of Pediatrics and Clinical Research, National Shimoshizu Hospital, Yotsukaido, Chiba 284, Japan.
Immunization of AKR/N mice with murine fibroblasts, transfected with the TSH receptor (TSHR) and a murine major histocompatibility complex class II molecule having the same H-2k haplotype (but not either alone), induces immune thyroid disease with the humoral and histological features of human Graves’, including the presence of two different TSHR antibodies (TSHRAbs): stimulating TSHRAbs, which cause hyperthyroidism; and TSH-binding-inhibiting immunoglobulins. The primary functional epitope for both types of antibodies in Graves’ patients is on the N-terminal portion of the extracellular domain of the TSHR, residues 25 to 165; most require residues 90–165 to express TSHRAb activity, as evidenced in studies using chimeras of the TSHR and lutropin-choriogonadotropin receptor (LH-CGR). To evaluate the role of this region of the TSHR in the formation of Graves’ TSHRAbs, we immunized AKR/N mice with fibroblasts transfected with three human TSHR chimeras with residues 9–165 (Mc1+2), 90–165 (Mc2), or 261–370 (Mc4) substituted by equivalent residues of the rat LH-CGR. Mice immunized with the Mc1+2 and Mc2 chimeras, with the N-terminal portion of the extracellular domain of the TSHR substituted by LH-CGR residues, did not develop TSHRAbs. Mice immunized with the Mc4 chimera, having a major portion of the C-terminal portion of the extracellular domain of the TSHR replaced by comparable LH-CGR residues, can develop TSHRAbs. The results suggest that the N-terminal segment of the TSHR extracellular domain is not only a critical functional epitope for Graves’ TSHRAbs, but it is important also in their formation in a mouse model of Graves’ disease.
This article has been cited by other articles:
 |
|
 |
|
  O. Martinez, E. Gangi, D. Mordi, S. Gupta, S. Dorevitch, M.-P. Lefranc, and B. S. Prabhakar Diversity in the Complementarity-Determining Region 3 (CDR3) of Antibodies from Mice with Evolving Anti-Thyroid-Stimulating Hormone Receptor Antibody Responses Endocrinology, February 1, 2007; 148(2): 752 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. McLachlan, Y. Nagayama, and B. Rapoport Insight into Graves' Hyperthyroidism from Animal Models Endocr. Rev., October 1, 2005; 26(6): 800 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Muehlberg, J. A. Gilbert, P. V. Rao, A. M. McGregor, and J. P. Banga Dynamics of Thyroid-Stimulating and -Blocking Antibodies to the Thyrotropin Receptor in a Murine Model of Graves' Disease Endocrinology, April 1, 2004; 145(4): 1539 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Prabhakar, R. S. Bahn, and T. J. Smith Current Perspective on the Pathogenesis of Graves' Disease and Ophthalmopathy Endocr. Rev., December 1, 2003; 24(6): 802 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Schwarz-Lauer, P. N. Pichurin, C.-R. Chen, Y. Nagayama, C. Paras, J. C. Morris, B. Rapoport, and S. M. McLachlan The Cysteine-Rich Amino Terminus of the Thyrotropin Receptor Is the Immunodominant Linear Antibody Epitope in Mice Immunized Using Naked Deoxyribonucleic Acid or Adenovirus Vectors Endocrinology, May 1, 2003; 144(5): 1718 - 1725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. Rao, P. F. Watson, A. P. Weetman, G. Carayanniotis, and J. P. Banga Contrasting Activities of Thyrotropin Receptor Antibodies in Experimental Models of Graves' Disease Induced by Injection of Transfected Fibroblasts or Deoxyribonucleic Acid Vaccination Endocrinology, January 1, 2003; 144(1): 260 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nagayama, M. Kita-Furuyama, T. Ando, K. Nakao, H. Mizuguchi, T. Hayakawa, K. Eguchi, and M. Niwa A Novel Murine Model of Graves' Hyperthyroidism with Intramuscular Injection of Adenovirus Expressing the Thyrotropin Receptor J. Immunol., March 15, 2002; 168(6): 2789 - 2794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Park, H. Kim, J. M. Suh, S. J. Park, S. H. You, H. K. Chung, K. W. Lee, O-Y. Kwon, B. Y. Cho, Y. K. Kim, et al. Involvement of JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) in the Thyrotropin Signaling Pathway Mol. Endocrinol., May 1, 2000; 14(5): 662 - 670. [Abstract] [Full Text]
|
|
|
|
|
|
S. Kaithamana, J. Fan, Y. Osuga, S.-G. Liang, and B. S. Prabhakar Induction of Experimental Autoimmune Graves' Disease in BALB/c Mice J. Immunol., November 1, 1999; 163(9): 5157 - 5164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kita, L. Ahmad, R. C. Marians, H. Vlase, P. Unger, P. N. Graves, and T. F. Davies Regulation and Transfer of a Murine Model of Thyrotropin Receptor Antibody Mediated Graves' Disease Endocrinology, March 1, 1999; 140(3): 1392 - 1398. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Wortsman, P. McConnachie, K. Tahara, and L. D. Kohn Thyrotropin Receptor Epitopes Recognized by Graves' Autoantibodies Developing under Immunosuppressive Therapy J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2302 - 2308. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
