{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T13:13:27Z","timestamp":1783516407706,"version":"3.55.0"},"reference-count":45,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Animal models of Graves\u2019 disease have been generated in recent years with various vaccination protocols using wild-type TSH receptor. In this study, we report the findings of genetic immunization of Swiss outbred mice with three different mutated human TSH receptor plasmids, each containing one constitutive activating mutation located at the ectodomain (S281N), exoloop (I486F), and transmembrane segment (D633H) respectively. Although the overall rate of thyrotoxicosis in the mice was &amp;lt; 10%, anti-TSH receptor antibodies could be detected in many animals by flow cytometry, radioreceptor assay, and functional bioassays using recombinant human TSH receptor. Mice injected with plasmids harboring activated mutants (S281N and D633H) showed production of predominantly stimulating antibodies, whilst those treated with wild-type receptor plasmids generated mainly blocking sera. Most of these antibodies displaced radiolabeled bovine TSH, and their epitopes, independent of functional characteristics, were mapped to the first 271 amino acids of the TSH receptor. This supports recent findings that binding of stimulatory or blocking antibodies lie in close proximity within the leucine-rich repeat region.<\/jats:p>","DOI":"10.1677\/jme-06-0027","type":"journal-article","created":{"date-parts":[[2007,2,9]],"date-time":"2007-02-09T11:33:01Z","timestamp":1171020781000},"page":"277-288","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":1,"title":["Effects of genetic immunization of Swiss outbred mice with human thyroid stimulating hormone receptor cDNA plasmids harboring gain-of-function mutations"],"prefix":"10.1530","volume":"38","author":[{"given":"Su-Chin","family":"Ho","sequence":"first","affiliation":[{"name":"SingHealth Research Facilities, Singapore Health Service, 5, Hospital Drive, Block A, #03-04, Singapore 169609, Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui-Sin","family":"Goh","sequence":"additional","affiliation":[{"name":"SingHealth Research Facilities, Singapore Health Service, 5, Hospital Drive, Block A, #03-04, Singapore 169609, Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene H C","family":"Kee","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology, Experimental Surgery and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierce K H","family":"Chow","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology, Experimental Surgery and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Pin","family":"Yeo","sequence":"additional","affiliation":[{"name":"Pathology, Singapore General Hospital, Outram Road, Singapore 169608, Republic of Singapore 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne H C","family":"Khoo","sequence":"additional","affiliation":[{"name":"SingHealth Research Facilities, Singapore Health Service, 5, Hospital Drive, Block A, #03-04, Singapore 169609, Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2006,12,12]]},"reference":[{"key":"2026070808152561400_ANDO-ETAL-2004","doi-asserted-by":"crossref","unstructured":"Ando\n              T\n            \n          , Latif R, Daniel S, Eguchi K & Davies TF 2004 Dissecting linear and conformational epitopes on the native thyrotropin receptor. 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Molecular Endocrinology9725\u2013733.","DOI":"10.1210\/mend.9.6.8592518"},{"key":"2026070808152561400_PARMA-ETAL-1997","doi-asserted-by":"crossref","unstructured":"Parma\n              J\n            \n          , Duprez L, Van Sande J, Hermans J, Rocmans P, Van Vliet G, Costagliola S, Rodien P, Dumont JE & Vassart G 1997 Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. Journal of Clinical Endocrinology and Metabolism822695\u20132701.","DOI":"10.1210\/jcem.82.8.4144"},{"key":"2026070808152561400_PICHURIN-ETAL-2002","doi-asserted-by":"crossref","unstructured":"Pichurin\n              B\n            \n          , Pichurina SM, Chazenbalk GD, Paras C, Chen CR, Rapoport B & McLachlan SM 2002 Immune deviation away from Th1 in interferon-gamma knockout mice does not enhance TSH receptor antibody production after naked DNA vaccination. 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Thyroid7867\u2013877.","DOI":"10.1089\/thy.1997.7.867"},{"key":"2026070808152561400_TONACCHERA-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Tonacchera\n              M\n            \n          , Vitti P, Agretti P, Giulianetti B, Mazzi B, Cavaliere R, Ceccarini G, Fiore E, Viacava P, Naccarato A et al.1998 Activating thyrotropin receptor mutations in histologically heterogeneous hyperfunctioning nodules of multinodular goiter. Thyroid8559\u2013564.","DOI":"10.1089\/thy.1998.8.559"},{"key":"2026070808152561400_VLAEMINCK-GUILLEM-ETAL-2002","doi-asserted-by":"crossref","unstructured":"Vlaeminck-Guillem\n              V\n            \n          , Ho SC, Rodien P, Vassart G & Costagliola S 2002 Activation of the cAMP pathway by the TSH receptor involves switching of the ectodomain from a tethered inverse agonist to an agonist. 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