Cerebral cortex hyperthyroidism of newborn Mct8-deficient mice transiently suppressed by Lat2 inactivation
Publisher
Public Library of ScienceDate
2014-05-12Citation
10.1371/journal.pone.0096915
Plos One 9.5 (2014): e96915
ISSN
1932-6203DOI
10.1371/journal.pone.0096915Funded by
Supported by grants from the Plan Nacional de Investigacion Cientıfica SAF2011-25608 (to JB), SAF2012-32491 (to MJO), SAF2009-120606-C02-01 and 02 and SAF2012-40080-C02-01 to (to MP and VN); Fundacion ARECES (to BM): intramural grants 09/708.1 and 10/708.1 from the CIBERER, Instituto Carlos III, Spain (to JB, MP and VN); Generalitat de Catalunya SGR2009-1490 (to VN) and SGR2009-1355 (to MP); Comunidad de Madrid S2010/BMD-2423 (to MJO); the USA National Institutes of Health, DK15070 and DK091016 (to AMDProject
Comunidad de Madrid. S2010/BMD-2423/MOIREditor's Version
http://dx.doi.org/10.1371/journal.pone.0096915Subjects
Thyroid hormone; MCT8; Cerebral cortex; MedicinaRights
© 2014 Núñez et al.Abstract
Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone
transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) 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 Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As
described previously the single Mct8 KO neonates had a transient increase of 3,5,39-triiodothyronine concentration and
expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO
prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On
postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex
3,5,39-triiodothyronine concentration and Hr 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
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Google Scholar:Núñez, Bárbara
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Martínez de Mena, Raquel
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Obregon, Maria Jesus
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Font-Llitjós, Mariona
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Nunes, Virginia
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Palacín, Manuel
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Dumitrescu, Alexandra M.
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Morte, Beatriz
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Bernal, Juan
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