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000008812 02470 $$ahttps://doi.org/10.1371/journal.pone.0096915$$2doi
000008812 037__ $$aTEXTUAL
000008812 037__ $$bArticle
000008812 041__ $$aeng
000008812 245__ $$aCerebral Cortex Hyperthyroidism of Newborn Mct8-Deficient Mice Transiently Suppressed by Lat2 Inactivation
000008812 269__ $$a2014-05-12
000008812 336__ $$aArticle
000008812 520__ $$a<p>Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, <em>MCT8</em> (<em>Monocarboxylate Transporter 8, SLC16A2</em>) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated <em>Lat2<sup>-/-</sup></em>, and <em>Mct8<sup>-/y</sup>Lat2</em><sup>-/-</sup> mice, to compare with wild type and <em>Mct8<sup>-/y</sup></em> mice during postnatal development. As described previously the single <em>Mct8</em> KO neonates had a transient increase of 3,5,3′-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double <em>Mct8Lat2</em> KO prevented the effect of <em>Mct8</em> inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the <em>Mct8</em> KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3′-triiodothyronine concentration and <em>Hr</em> expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.</p>
000008812 536__ $$oPlan Nacional de Investigación Científica$$cSAF2011-25608
000008812 536__ $$oPlan Nacional de Investigación Científica$$cSAF2012-32491
000008812 536__ $$oPlan Nacional de Investigación Científica$$cSAF2009-120606-C02-01
000008812 536__ $$oPlan Nacional de Investigación Científica$$cSAF2009-120606-C02-02
000008812 536__ $$oPlan Nacional de Investigación Científica$$cSAF2012-40080-C02-01
000008812 536__ $$oFundación ARECES
000008812 536__ $$oCIBERER, Instituto Carlos III, Spain$$c09/708.1
000008812 536__ $$oCIBERER, Instituto Carlos III, Spain$$c10/708.1
000008812 536__ $$oGeneralitat de Catalunya$$cSGR2009-1490
000008812 536__ $$oGeneralitat de Catalunya$$cSGR2009-1355
000008812 536__ $$oComunidad de Madrid$$cS2010/BMD-2423
000008812 536__ $$oNational Institutes of Health$$cDK15070
000008812 536__ $$oNational Institutes of Health$$cDK091016
000008812 540__ $$a<p>© 2014 Núñez et al.</p> <p>This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>
000008812 542__ $$fCC BY
000008812 690__ $$aBiological Sciences Division
000008812 691__ $$aMedicine
000008812 7001_ $$aNúñez, Bárbara$$uUniversidad Autónoma de Madrid
000008812 7001_ $$aMartínez de Mena, Raquel$$uUniversidad Autónoma de Madrid
000008812 7001_ $$aObregon, Maria Jesus$$uUniversidad Autónoma de Madrid
000008812 7001_ $$aFont-Llitjós, Mariona$$uCenter for Biomedical Research on Rare Diseases
000008812 7001_ $$aNunes, Virginia$$uLaboratorio de Genètica Molecular
000008812 7001_ $$aManuel Palacín$$uInstitute for Research in Biomedicine
000008812 7001_ $$aDumitrescu, Alexandra M.$$uUniversity of Chicago
000008812 7001_ $$aMorte, Beatriz$$uUniversidad Autónoma de Madrid
000008812 7001_ $$aBernal, Juan$$uUniversidad Autónoma de Madrid
000008812 773__ $$tPLOS ONE
000008812 8564_ $$yArticle$$9d732975d-11b0-46e1-8cf8-678a46192a4d$$s755325$$uhttps://knowledge.uchicago.edu/record/8812/files/journal.pone.0096915.pdf$$ePublic
000008812 909CO $$ooai:uchicago.tind.io:8812$$pGLOBAL_SET
000008812 983__ $$aArticle