{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:53:54Z","timestamp":1783486434222,"version":"3.55.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Abs that stimulate the thyrotropin receptor (TSHR), the cause of Graves\u2019 hyperthyroidism, only develop in humans. TSHR Abs can be induced in mice by immunization, but studying pathogenesis and therapeutic intervention requires a model without immunization. Spontaneous, iodine-accelerated, thyroid autoimmunity develops in NOD.H2h4 mice associated with thyroglobulin and thyroid-peroxidase, but not TSHR, Abs. We hypothesized that transferring the human TSHR A-subunit to NOD.H2h4 mice would result in loss of tolerance to this protein. BALB\/c human TSHR A-subunit mice were bred to NOD.H2h4 mice, and transgenic offspring were repeatedly backcrossed to NOD.H2h4 mice. All offspring developed Abs to thyroglobulin and thyroid-peroxidase. However, only TSHR-transgenic NOD.H2h4 mice (TSHR\/NOD.H2h4) developed pathogenic TSHR Abs as detected using clinical Graves\u2019 disease assays. As in humans, TSHR\/NOD.H2h4 female mice were more prone than male mice to developing pathogenic TSHR Abs. Fortunately, in view of the confounding effect of excess thyroid hormone on immune responses, spontaneously arising pathogenic human TSHR Abs cross-react poorly with the mouse TSHR and do not cause thyrotoxicosis. In summary, the TSHR\/NOD.H2h4 mouse strain develops spontaneous, iodine-accelerated, pathogenic TSHR Abs in female mice, providing a unique model to investigate disease pathogenesis and test novel TSHR Ag-specific immunotherapies aimed at curing Graves\u2019 disease in humans.<\/jats:p>","DOI":"10.4049\/jimmunol.1500126","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T08:46:26Z","timestamp":1427877986000},"page":"4154-4161","source":"Crossref","is-referenced-by-count":33,"title":["A Unique Mouse Strain That Develops Spontaneous, Iodine-Accelerated, Pathogenic Antibodies to the Human Thyrotrophin Receptor"],"prefix":"10.1093","volume":"194","author":[{"given":"Basil","family":"Rapoport","sequence":"first","affiliation":[{"name":"Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute\/David Geffen School of Medicine at University of California , Los Angeles, Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly A","family":"Aliesky","sequence":"additional","affiliation":[{"name":"Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute\/David Geffen School of Medicine at University of California , Los Angeles, Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Banuelos","sequence":"additional","affiliation":[{"name":"Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute\/David Geffen School of Medicine at University of California , Los Angeles, Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute\/David Geffen School of Medicine at University of California , Los Angeles, Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M","family":"McLachlan","sequence":"additional","affiliation":[{"name":"Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute\/David Geffen School of Medicine at University of California , Los Angeles, Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,5,1]]},"reference":[{"key":"2025030706183943100_r1","first-page":"673","article-title":"The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies","volume":"19","author":"Rapoport","year":"1998","journal-title":"Endocr. 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