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In several cases, frameshift and\/or nonsense mutations in TSHR were found in the patients with congenital hypothyroidism (CH), however they have not been functionally studied in an animal model. In the present work, we generated a unique <jats:italic>Tshr<\/jats:italic><jats:sup>\n                  <jats:italic>Df\/Df<\/jats:italic>\n                <\/jats:sup> rat model that recapitulates the phenotypes in TSHR Y444X patient by CRISPR\/Cas genome editing technology. In this rat model, TSHR is truncated at the second transmembrane domain, leading to CH phenotypes as what was observed in the patients, including dwarf, thyroid aplasia, infertility, TSH resistant as well as low serum thyroid hormone levels. The phenotypes can be reversed, at least partially, by levothyroxine (L-T4) treatment after weaning. The thyroid development is severely impaired in the <jats:italic>Tshr<\/jats:italic><jats:sup>\n                  <jats:italic>Df\/Df<\/jats:italic>\n                <\/jats:sup> rats due to the suppression of the thyroid specific genes, i.e., thyroperoxidase (<jats:italic>Tpo<\/jats:italic>), thyroglobulin (<jats:italic>Tg<\/jats:italic>) and sodium iodide symporter (<jats:italic>Nis<\/jats:italic>), at both mRNA and protein levels. In conclusion, the <jats:italic>Tshr<\/jats:italic><jats:sup>\n                  <jats:italic>Df\/Df<\/jats:italic>\n                <\/jats:sup> rat serves as a brand new genetic model to study CH in human, and will greatly help to shed light into the development of terminal organs that are sensitive to thyroid hormones.<\/jats:p>","DOI":"10.1038\/s41598-018-22405-7","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T15:06:30Z","timestamp":1519743990000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Generation and characterization of a hypothyroidism rat model with truncated thyroid stimulating hormone receptor"],"prefix":"10.1038","volume":"8","author":[{"given":"Jianqiang","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5235-6410","authenticated-orcid":false,"given":"Guoping","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianmin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,3,5]]},"reference":[{"key":"22405_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-17","volume":"5","author":"MV Rastogi","year":"2010","unstructured":"Rastogi, M. 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