{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:33:07Z","timestamp":1781796787996,"version":"3.54.5"},"reference-count":29,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"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":[[2021,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Mutations of the thyroid hormone receptor \u03b1 (\n                      <jats:italic toggle=\"yes\">THRA<\/jats:italic>\n                      ) gene cause resistance to thyroid hormone (RTH\u03b1). RTH\u03b1 patients exhibit very mild abnormal thyroid function test results (serum triiodothyronine can be high-normal to high; thyroxine normal to low; thyrotropin is normal or mildly raised) but manifest hypothyroid symptoms with growth retardation, delayed bone development, and anemia. Much has been learned about the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      molecular actions in TR\u03b11 mutants affecting abnormal growth, bone development, and anemia by using a mouse model of RTH\u03b1 (\n                      <jats:italic toggle=\"yes\">\n                        Thra1\n                        <jats:sup>PV\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mice). However, it is not clear whether TR\u03b11 mutants affect lymphopoiesis in RTH\u03b1 patients. The present study addressed the question of whether TR\u03b11 mutants could cause defective lymphopoiesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We assessed lymphocyte abundance in the peripheral circulation and in the lymphoid organs of\n                      <jats:italic toggle=\"yes\">\n                        Thra1\n                        <jats:sup>PV\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mice. We evaluated the effect of thyroid hormone on B cell development in the bone and spleen of these mice. We identified key transcription factors that are directly regulated by TR\u03b11 in the regulation of B cell development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">:<\/jats:italic>\n                      Compared with wild-type mice, a significant reduction in B cells, but not in T cells, was detected in the peripheral circulation, bone marrow, and spleen of\n                      <jats:italic toggle=\"yes\">\n                        Thra1\n                        <jats:sup>PV\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mice. The expression of key transcription regulators of B cell development, such as\n                      <jats:italic toggle=\"yes\">Ebf1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Tcf3<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Pax<\/jats:italic>\n                      5, was significantly decreased in the bone marrow and spleen of\n                      <jats:italic toggle=\"yes\">\n                        Thra1\n                        <jats:sup>PV\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mice. We further elucidated that the\n                      <jats:italic toggle=\"yes\">Ebf1<\/jats:italic>\n                      gene, essential for lineage specification in the early B cell development, was directly regulated by TR\u03b11. Thus, mutations of TR\u03b11 could impair B cell development in the bone marrow via suppression of key regulators of B lymphopoiesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:italic toggle=\"yes\">Conclusions<\/jats:italic>\n                      :\n                    <\/jats:title>\n                    <jats:p>\n                      Analysis of lymphopoiesis in a mouse model of RTH\u03b1 showed that B cell lymphopoiesis was suppressed by TR\u03b11 mutations. The suppressed development of B cells was, at least in part, via inhibition of the expression of key regulators,\n                      <jats:italic toggle=\"yes\">Ebf1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Tcf3<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Pax<\/jats:italic>\n                      5, by TR\u03b11 mutations. These findings suggest that the mutations of the\n                      <jats:italic toggle=\"yes\">THRA<\/jats:italic>\n                      gene in patients could lead to B cell deficiency.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2019.0782","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T02:10:46Z","timestamp":1606961446000},"page":"994-1002","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Thyroid Hormone Receptor \u03b11 Mutants Impair B Lymphocyte Development in a Mouse Model"],"prefix":"10.1177","volume":"31","author":[{"given":"Sunmi","family":"Park","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuguang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjun","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheue-Yann","family":"Cheng","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0007"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.143"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006991"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1113940"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00840"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.1.152"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261565798"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.11.003"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067954"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00033a034"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-500272"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035877"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.230285997"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.5.1213"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702409104"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115728"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.0112.x"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/502751"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.293"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80078-3"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112422"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90076-0"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/376263a0"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/44076"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.8.3334"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7209519"},{"key":"e_1_3_5_28_2","first-page":"129","article-title":"Identification of a point mutation in the thyrotropin receptor of the hyt\/hyt hypothyroid mouse","volume":"8","author":"Stein SA","year":"1994","unstructured":"Stein SA, , Oates EL, , Hall CR, , Grumbles RM, , Fernandez LM, , Taylor NA, , Puett D, , Jin S. 1994. Identification of a point mutation in the thyrotropin receptor of the hyt\/hyt hypothyroid mouse. Mol Endocrinol, 8:129\u2013138.","journal-title":"Mol Endocrinol"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.6.2712"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-19-0339"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2019.0782","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2019.0782","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2019.0782","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:06:55Z","timestamp":1777586815000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2019.0782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1089\/thy.2019.0782"],"URL":"https:\/\/doi.org\/10.1089\/thy.2019.0782","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6]]}}}