{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:54:09Z","timestamp":1773276849202,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T00:00:00Z","timestamp":1513900800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T00:00:00Z","timestamp":1513900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"Abstract<\/jats:title>Thyroid hormone receptor \u03b1 (THRA)<\/jats:italic> gene mutations, via dominant negative mode, cause erythroid abnormalities in patients. Using mice expressing a dominant negative TR\u03b11 mutant (TR\u03b11PV; Thra1<\/jats:italic>\n PV<\/jats:italic>\/+<\/jats:sup> mice), we showed that TR\u03b11PV acted directly to suppress the expression of key erythroid genes, causing erythroid defects. The nuclear receptor corepressor 1 (NCOR1) was reported to mediate the dominant negative effects of mutated TR\u03b11. However, how NCOR1 could regulate TR\u03b11 mutants in erythroid defects in vivo<\/jats:italic> is not known. In the present study, we crossed Thra1<\/jats:italic>\n PV<\/jats:italic>\/+<\/jats:sup> mice with mice expressing a mutant Ncor1<\/jats:italic> allele (NCOR1\u0394ID<\/jats:italic>; Ncor1<\/jats:italic>\n \u0394ID<\/jats:italic>\n <\/jats:sup> mice). TR\u03b11PV mutant cannot bind to NCOR1\u0394ID. The expression of NCOR1\u0394ID ameliorated abnormalities in the peripheral blood indices, and corrected the defective differentiation potential of progenitors in the erythroid lineage. The defective terminal erythropoiesis of lineage-negative bone marrow cells of Thra1<\/jats:italic>\n PV<\/jats:italic>\/+<\/jats:sup> mice was rescued by the expression of NCOR1\u0394ID. De-repression of key erythroid genes in Thra1<\/jats:italic>\n PV<\/jats:italic>\/+<\/jats:sup>Ncor1<\/jats:italic>\u0394ID<\/jats:italic>\/\u0394ID<\/jats:italic>\n <\/jats:sup> mice led to partial rescue of terminal erythroid differentiation. These results indicate that the inability of TR\u03b11PV to recruit NCOR1\u0394ID to form a repressor complex relieved the deleterious actions of TR\u03b11 mutants in vivo<\/jats:italic>. NCOR1 is a critical novel regulator underpining the pathogenesis of erythroid abnormalities caused by TR\u03b11 mutants.<\/jats:p>","DOI":"10.1038\/s41598-017-18409-4","type":"journal-article","created":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T14:23:03Z","timestamp":1513606983000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["NCOR1 modulates erythroid disorders caused by mutations of thyroid hormone receptor \u03b11"],"prefix":"10.1038","volume":"7","author":[{"given":"Cho Rong","family":"Han","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunmi","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheue-yann","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,12,22]]},"reference":[{"key":"18409_CR1","doi-asserted-by":"publisher","first-page":"3876","DOI":"10.1016\/j.bbagen.2012.07.001","volume":"1830","author":"I Astapova","year":"2013","unstructured":"Astapova, I. & Hollenberg, A. 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Mice with a targeted mutation in the thyroid hormone beta receptor gene exhibit impaired growth and resistance to thyroid hormone. Proceedings of the National Academy of Sciences of the United States of America \n 97, 13209\u201313214, https:\/\/doi.org\/10.1073\/pnas.230285997 (2000).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"18409_CR4","doi-asserted-by":"publisher","first-page":"15095","DOI":"10.1073\/pnas.261565798","volume":"98","author":"M Kaneshige","year":"2001","unstructured":"Kaneshige, M. et al. A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice. 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