{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:22:14Z","timestamp":1777875734045,"version":"3.51.4"},"reference-count":47,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Graves' disease, caused by autoantibodies that activate the thyrotropin (TSH) receptor (TSHR), has only been reported in humans. Thyroiditis-prone NOD.\n                      <jats:italic toggle=\"yes\">\n                        H2\n                        <jats:sup>h4<\/jats:sup>\n                      <\/jats:italic>\n                      mice develop autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO) but not to the TSHR. Evidence supports the importance of the shed TSHR A-subunit in the initiation and\/or amplification of the autoimmune response to the holoreceptor. Cells expressing the gene for the isolated A-subunit secrete A-subunit protein, a surrogate for holoreceptor A-subunit shedding. NOD.\n                      <jats:italic toggle=\"yes\">\n                        H2\n                        <jats:sup>h4<\/jats:sup>\n                      <\/jats:italic>\n                      mice with the\n                      <jats:italic toggle=\"yes\">human<\/jats:italic>\n                      TSHR A-subunit targeted to the thyroid (a \u201cself\u201d antigen in such transgenic (Tgic) animals), unlike their wild-type (wt) siblings, spontaneously develop pathogenic TSHR antibodies to the human-TSH holoreceptor. These autoantibodies do not recognize the endogenous mouse-TSH holoreceptor and do not cause hyperthyroidism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We have now generated NOD.\n                      <jats:italic toggle=\"yes\">\n                        H2\n                        <jats:sup>h4<\/jats:sup>\n                      <\/jats:italic>\n                      mice with the\n                      <jats:italic toggle=\"yes\">mouse<\/jats:italic>\n                      -TSHR A-subunit transgene targeted to the thyroid. Tgic mice and wt littermates were compared for intrathyroidal expression of the mouse A-subunit. Sera from six-month-old mice were tested for the presence of autoantibodies to Tg and TPO as well as for pathogenic TSHR antibodies (TSH binding inhibition, bioassay for thyroid stimulating antibodies) and nonpathogenic TSHR antibodies (ELISA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Expression of the\n                      <jats:italic toggle=\"yes\">mouse<\/jats:italic>\n                      TSHR A-subunit transgene in the thyroid was confirmed by real-time polymerase chain reaction in the Tgics and had no effect on the spontaneous development of autoantibodies to Tg or TPO. However, unlike the same NOD.\n                      <jats:italic toggle=\"yes\">\n                        H2\n                        <jats:sup>h4<\/jats:sup>\n                      <\/jats:italic>\n                      strain with the\n                      <jats:italic toggle=\"yes\">human<\/jats:italic>\n                      -TSHR A-subunit target to the thyroid, mice expressing intrathyroidal\n                      <jats:italic toggle=\"yes\">mouse<\/jats:italic>\n                      -TSHR A subunit failed to develop either pathogenic or nonpathogenic TSHR antibodies. The mouse TSHR A-subunit differs from the human TSHR A-subunit in terms of its amino acid sequence and has one less glycosylation site than the human TSHR A-subunit.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Multiple genetic and environmental factors contribute to the pathogenesis of Graves' disease. The present study suggests that the TSHR A-subunit structure (possibly including posttranslational modification such as glycosylation) may explain, in part, why Graves' disease only develops in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2019.0260","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T07:21:19Z","timestamp":1560237679000},"page":"1138-1146","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["A Mouse Thyrotropin Receptor A-Subunit Transgene Expressed in Thyroiditis-Prone Mice May Provide Insight into Why Graves' Disease Only Occurs in Humans"],"prefix":"10.1177","volume":"29","author":[{"given":"Sandra M.","family":"McLachlan","sequence":"first","affiliation":[{"name":"Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute, Los Angeles, California."},{"name":"UCLA School of Medicine, University of California, Los Angeles, California."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly A.","family":"Aliesky","sequence":"additional","affiliation":[{"name":"Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute, Los Angeles, California."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basil","family":"Rapoport","sequence":"additional","affiliation":[{"name":"Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute, Los Angeles, California."},{"name":"UCLA School of Medicine, University of California, Los Angeles, California."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,8,19]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2007.0170"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2015.07.009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1408821111"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr247"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-012-9703-2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2011.0209"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1717"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2013-1055"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ai.2014.11.001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1996.0191"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1999.0272"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1998.1446"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0321"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500126"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(82)80176-2"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)80169-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi961359w"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(99)00018-0"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215745"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200317069"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2015-1098"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18959"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-01048"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.1.668"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-0069"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13866-4"},{"key":"e_1_3_3_28_2","first-page":"63","article-title":"Aberrant iodide autoregulation induces hypothyroidism in a mouse strain in the absence of thyroid autoimmunity","volume":"29","author":"McLachlan SM","year":"2017","unstructured":"McLachlan SM, , Aliesky HA, , Rapoport B. 2017. 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