{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T08:05:28Z","timestamp":1786781128508,"version":"build-2736575974"},"reference-count":39,"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                      The monocarboxylate transporter 8 (Mct8) protein is a primary thyroxine (T4) and triiodothyronine (T3) (thyroid hormone [TH]) transporter. Mutations of the MCT8-encoding,\n                      <jats:italic toggle=\"yes\">SLC16A2<\/jats:italic>\n                      gene alter thyroid function and TH metabolism and severely impair neurodevelopment (Allan-Herndon-Dudley syndrome [AHDS]). Mct8-deficient mice manifest thyroid alterations but lack neurological signs. It is believed that Mct8 deficiency in mice is compensated by T4 transport through the\n                      <jats:italic toggle=\"yes\">Slco1c1<\/jats:italic>\n                      -encoded organic anion transporter polypeptide 1c1 (Oatp1c1). This allows local brain generation of sufficient T3 by the\n                      <jats:italic toggle=\"yes\">Dio2<\/jats:italic>\n                      -encoded type 2 deiodinase, thus preventing brain hypothyroidism. The\n                      <jats:italic toggle=\"yes\">Slc16a2<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">Slco1c1<\/jats:italic>\n                      (MO) and\n                      <jats:italic toggle=\"yes\">Slc16a2<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">Dio2<\/jats:italic>\n                      (MD) double knockout (KO) mice lacking T4 and T3 transport, or T3 transport and T4 deiodination, respectively, should be appropriate models of AHDS. Our goal was to compare the cerebral hypothyroidism of systemic hypothyroidism (SH) caused by thyroid gland blockade with that present in the double KO mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We performed RNA sequencing by using RNA from the cerebral cortex and striatum of SH mice and the double KO mice on postnatal days 21\u201323. Real-time polymerase chain reaction was used to confirm RNA-Seq results in replicate biological samples. Cell type involvement was assessed from cell type-enriched genes. Functional genomic differences were analyzed by functional node activity based on a probabilistic graphical model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Each of the three conditions gave a different pattern of gene expression, with partial overlaps. SH gave a wider and highest variation of gene expression than MD or MO. This was partially due to secondary gene responses to hypothyroidism. The set of primary transcriptional T3 targets showed a tighter overlap, but quantitative gene responses indicated that the gene responses in SH were more severe than in MD or MO. Examination of cell type-enriched genes indicated cellular differences between the three conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The results indicate that the neurological impairment of AHDS is too severe to be fully explained by TH deprivation only.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2020.0649","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T04:09:33Z","timestamp":1607918973000},"page":"985-993","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["Brain Gene Expression in Systemic Hypothyroidism and Mouse Models of MCT8 Deficiency: The Mct8-Oatp1c1-Dio2 Triad"],"prefix":"10.1177","volume":"31","author":[{"given":"Beatriz","family":"Morte","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid, Center for Biomedical Research on Rare Diseases (Ciberer U708), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Gil-Iba\u00f1ez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid, Center for Biomedical Research on Rare Diseases (Ciberer U708), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Heuer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Bernal","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid, Center for Biomedical Research on Rare Diseases (Ciberer U708), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.66"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnz008"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0378"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1616"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.04.002"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/380999"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17226-7"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30153-4"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/431313"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2162"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2001-0309"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0058"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-019-01896-8"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-013-0645-0"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0595"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0944"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70324"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.22487"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0068"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0900"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0390"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.12.0740"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28253"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1633"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7902-8_3"},{"key":"e_1_3_6_27_2","first-page":"706","article-title":"Global transcriptome analysis of primary cerebrocortical cells: identification of genes regulated by triiodothyronine in specific cell types","volume":"27","author":"Gil-Ibanez P","year":"2017","unstructured":"Gil-Ibanez P, , Garcia-Garcia F, , Dopazo J, , Bernal J, , Morte B. 2017. Global transcriptome analysis of primary cerebrocortical cells: identification of genes regulated by triiodothyronine in specific cell types. Cereb Cortex, 27:706\u2013717.","journal-title":"Cereb Cortex"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.2144\/000113388"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-03084"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25496"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v037.i01"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6614-4-S1-S7"},{"key":"e_1_3_6_35_2","unstructured":"Salas-Lucia F Pacheco-Torres J Alonso-Lopez E Moreno-Camu\u00f1as MM Berbel P. 2018. Gestational and early postnatal hypothyroidism arrests angiogenesis and glymphatic system development in the neocortex of rats. Abstract presented at the 41st Annual Meeting on European Thyroid Association Newcastle upon Tyne United Kingdom 2018. Abstract no. OP-11-37."},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0508"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2017.0024"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410124200"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2719"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135600"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2020.0649","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2020.0649","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2020.0649","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:07:54Z","timestamp":1777586874000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2020.0649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1089\/thy.2020.0649"],"URL":"https:\/\/doi.org\/10.1089\/thy.2020.0649","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6]]}}}