{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:14:55Z","timestamp":1783448095879,"version":"3.55.0"},"reference-count":39,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":2771,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Thyroid hemiagenesis, a rare congenital condition detected by ultrasound screening of the neck, is usually not manifested clinically in humans. This condition has been reported in mice with hypothyroidism associated with induced deficiency in paired box 8 and NK2 homeobox 1, sonic hedgehog, or T-box 1. Unexpectedly, we observed thyroid hemiagenesis in NOD.H2&amp;lt;sup&amp;gt;h4&amp;lt;\/sup&amp;gt; mice, an unusual strain that spontaneously develops iodide enhanced thyroid autoimmunity but remains euthyroid. Objectives and Methods: First, to compare mice with thyroid hemiagenesis versus bilobed littermates for serum T4, autoantibodies to thyroglobulin (ELISA) and thyroid peroxidase (TPO; flow cytometry with eukaryotic cells expressing mouse TPO), gross anatomy, and thyroid histology; second, to estimate the percentage of mice with thyroid hemiagenesis in the NOD.H2&amp;lt;sup&amp;gt;h4&amp;lt;\/sup&amp;gt; mice we have studied over 6 years. Results: Thyroid hemiagenesis was observed in 3 of 1,025 NOD.H2&amp;lt;sup&amp;gt;h4&amp;lt;\/sup&amp;gt; mice (2 females, 1 male; 0.3%). Two instances of hemiagenesis were in wild-type females and one in a transgenic male expressing the human TSHR A-subunit in the thyroid. Two mice had very large unilobed glands, as in some human cases with this condition. Thyroid lymphocytic infiltration, serum T4, and the levels of thyroid autoantibodies were similar in mice with thyroid hemiagenesis and bilobed littermates. Conclusions: Unlike hypothyroidism associated with hemiagenesis in transcription factor knockout mice, hemiagenesis in euthyroid NOD.H2&amp;lt;sup&amp;gt;h4&amp;lt;\/sup&amp;gt; mice occurs spontaneously and is phenotypically similar to that occasionally observed in humans.<\/jats:p>","DOI":"10.1159\/000490700","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T17:04:25Z","timestamp":1531933465000},"page":"187-192","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":2,"title":["Thyroid Hemiagenesis in a Thyroiditis Prone Mouse Strain"],"prefix":"10.1530","volume":"7","author":[{"given":"Sandra\u00a0M.","family":"McLachlan","sequence":"first","affiliation":[{"name":"1Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute, Los Angeles, California, USA"},{"name":"2UCLA School of Medicine, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly\u00a0A.","family":"Aliesky","sequence":"additional","affiliation":[{"name":"1Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Garcia","sequence":"additional","affiliation":[{"name":"1Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Banuelos","sequence":"additional","affiliation":[{"name":"1Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil","family":"Rapoport","sequence":"additional","affiliation":[{"name":"1Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute, Los Angeles, California, USA"},{"name":"2UCLA School of Medicine, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2018,7,18]]},"reference":[{"key":"2026070712562502400_ref1","doi-asserted-by":"crossref","unstructured":"Suzuki S, Midorikawa S, Matsuzuka T, Fukushima T, Ito Y, Shimura H, Takahashi H, Ohira T, Ohtsuru A, Abe M, Suzuki S, Yamashita S: Prevalence and Characterization of Thyroid Hemiagenesis in Japan: The Fukushima Health Management Survey. Thyroid 2017; 27: 1011\u20131016.","DOI":"10.1089\/thy.2016.0662"},{"key":"2026070712562502400_ref2","doi-asserted-by":"crossref","unstructured":"Maiorana R, Carta A, Floriddia G, Leonardi D, Buscema M, Sava L, Calaciura F, Vigneri R: Thyroid hemiagenesis: prevalence in normal children and effect on thyroid function. J Clin Endocrinol Metab 2003; 88: 1534\u20131536.","DOI":"10.1210\/jc.2002-021574"},{"key":"2026070712562502400_ref3","doi-asserted-by":"crossref","unstructured":"Szczepanek-Parulska E, Zybek-Kocik A, Wartofsky L, Ruchala M: Thyroid hemiagenesis: incidence, clinical significance, and genetic background. J Clin Endocrinol Metab 2017; 102: 3124\u20133137.","DOI":"10.1210\/jc.2017-00784"},{"key":"2026070712562502400_ref4","doi-asserted-by":"crossref","unstructured":"Baldini M, Orsatti A, Cantalamessa L: A singular case of Graves\u2019 disease in congenital thyroid hemiagenesis. 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Hum Mol Genet 2007; 16: 276\u2013285.","DOI":"10.1093\/hmg\/ddl455"},{"key":"2026070712562502400_ref8","doi-asserted-by":"crossref","unstructured":"Rasooly L, Burek CL, Rose NR: Iodine-induced autoimmune thyroiditis in NOD-H2h4 mice. Clin Immunol Immunopathol 1996; 81: 287\u2013292.","DOI":"10.1006\/clin.1996.0191"},{"key":"2026070712562502400_ref9","doi-asserted-by":"crossref","unstructured":"Braley-Mullen H, Sharp GC, Medling B, Tang H: Spontaneous autoimmune thyroiditis in NOD.H-2h4 mice. J Autoimmun 1999; 12: 157\u2013165.","DOI":"10.1006\/jaut.1999.0272"},{"key":"2026070712562502400_ref10","doi-asserted-by":"crossref","unstructured":"Hutchings PR, Verma S, Phillips JM, Harach SZ, Howlett S, Cooke A: Both CD4(+) T cells and CD8(+) T cells are required for iodine accelerated thyroiditis in NOD mice. Cell Immunol 1999; 192: 113\u2013121.","DOI":"10.1006\/cimm.1998.1446"},{"key":"2026070712562502400_ref11","doi-asserted-by":"crossref","unstructured":"Chen CR, Hamidi S, Braley-Mullen H, Nagayama Y, Bresee C, Aliesky HA, Rapoport B, McLachlan SM: Antibodies to thyroid peroxidase arise spontaneously with age in NOD.H-2h4 mice and appear after thyroglobulin antibodies. Endocrinology 2010; 151: 4583\u20134593.","DOI":"10.1210\/en.2010-0321"},{"key":"2026070712562502400_ref12","doi-asserted-by":"crossref","unstructured":"Rapoport B, Aliesky HA, Banuelos B, Chen CR, McLachlan SM: A unique mouse strain that develops spontaneous, iodine-accelerated, pathogenic antibodies to the human thyrotrophin receptor. 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Endocrinology 2004; 145: 228\u2013233.","DOI":"10.1210\/en.2003-1134"},{"key":"2026070712562502400_ref25","doi-asserted-by":"crossref","unstructured":"Schwarz-Lauer L, Pichurin PN, Chen C-R, Nagayama Y, Paras C, Morris JC, Rapoport B, McLachlan SM: 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 2003; 144: 1718\u20131725.","DOI":"10.1210\/en.2002-0069"},{"key":"2026070712562502400_ref26","doi-asserted-by":"crossref","unstructured":"McLachlan SM, Nagayama Y, Pichurin PN, Mizutori Y, Chen CR, Misharin A, Aliesky HA, Rapoport B: The link between Graves\u2019 disease and Hashimoto\u2019s thyroiditis: A role for regulatory T cells. Endocrinology 2007; 148: 5724\u20135733.","DOI":"10.1210\/en.2007-1024"},{"key":"2026070712562502400_ref27","doi-asserted-by":"crossref","unstructured":"Misharin A, Hewison M, Chen CR, Lagishetty V, Aliesky HA, Mizutori Y, Rapoport B, McLachlan SM: Vitamin D deficiency modulates Graves\u2019 hyperthyroidism induced in BALB\/c mice by thyrotropin receptor immunization. Endocrinology 2009; 150: 1051\u20131060.","DOI":"10.1210\/en.2008-1191"},{"key":"2026070712562502400_ref28","doi-asserted-by":"crossref","unstructured":"Chen CR, Aliesky H, Pichurin PN, Nagayama Y, McLachlan SM, Rapoport B: Susceptibility rather than resistance to hyperthyroidism is dominant in a thyrotropin receptor adenovirus-induced animal model of Graves\u2019 disease as revealed by BALB\/c-C57BL\/6 hybrid mice. Endocrinology 2004; 145: 4927\u20134933.","DOI":"10.1210\/en.2004-0716"},{"key":"2026070712562502400_ref29","doi-asserted-by":"crossref","unstructured":"Jaume JC, Guo J, Wang Y, Rapoport B, McLachlan SM: Cellular thyroid peroxidase (TPO), unlike purified TPO and adjuvant, induces antibodies in mice that resemble autoantibodies in human autoimmune thyroid disease. J Clin Endocrinol Metab 1999; 84: 1651\u20131657.","DOI":"10.1210\/jc.84.5.1651"},{"key":"2026070712562502400_ref30","doi-asserted-by":"crossref","unstructured":"Jaume JC, Rapoport B, McLachlan SM: Lack of female bias in a mouse model of autoimmune hyperthyroidism (Graves\u2019 disease). 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Pediatr Res 2005; 57: 908\u2013913.","DOI":"10.1203\/01.PDR.0000161409.04177.36"},{"key":"2026070712562502400_ref39","doi-asserted-by":"crossref","unstructured":"Szczepanek-Parulska E, Zybek-Kocik A, Wolinski K, Czarnocka B, Ruchala M: Does TSH trigger the anti-thyroid autoimmune processes? Observation on a large cohort of naive patients with thyroid hemiagenesis. Arch Immunol Ther Exp (Warsz) 2016; 64: 331\u2013338.","DOI":"10.1007\/s00005-016-0393-y"}],"container-title":["European Thyroid Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/490700","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/7\/4\/187\/34286\/etj490700.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/7\/4\/187\/34286\/etj490700.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:26:23Z","timestamp":1783445183000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article\/7\/4\/187\/4638\/Thyroid-Hemiagenesis-in-a-Thyroiditis-Prone-Mouse"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,18]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,8,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000490700","relation":{},"ISSN":["2235-0802","2235-0640"],"issn-type":[{"value":"2235-0802","type":"electronic"},{"value":"2235-0640","type":"print"}],"subject":[],"published":{"date-parts":[[2018,7,18]]}}}