Slc16a2

Summary

Gene Symbol: Slc16a2
Description: solute carrier family 16 (monocarboxylic acid transporters), member 2
Alias: AW105741, Mct8, Xpct, monocarboxylate transporter 8, MCT 8, Monocarboxylate transporter 8 (MCT 8) (X-linked PEST-containing transporter), X-linked PEST-containing transporter, solute carrier family 16 member 2
Species: mouse
Products:     Slc16a2

Top Publications

  1. Trajkovic Arsic M, Muller J, Darras V, Groba C, Lee S, Weih D, et al. Impact of monocarboxylate transporter-8 deficiency on the hypothalamus-pituitary-thyroid axis in mice. Endocrinology. 2010;151:5053-62 pubmed publisher
    In patients, inactivating mutations in the gene encoding the thyroid hormone-transporting monocarboxylate transporter 8 (Mct8) are associated with severe mental and neurological deficits and disturbed thyroid hormone levels...
  2. Di Cosmo C, Liao X, Dumitrescu A, Philp N, Weiss R, Refetoff S. Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion. J Clin Invest. 2010;120:3377-88 pubmed publisher
    ..Humans and mice deficient in monocarboxylate transporter 8 (MCT8) have low serum thyroxine (T4) levels that cannot be fully explained by increased deiodination...
  3. Wirth E, Roth S, Blechschmidt C, Holter S, Becker L, Racz I, et al. Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome. J Neurosci. 2009;29:9439-49 pubmed publisher
    ..Mutations in one of these, monocarboxylate transporter 8 (MCT8), have been identified as underlying cause for the Allan-Herndon-Dudley syndrome, an X-linked ..
  4. Di Cosmo C, Liao X, Dumitrescu A, Weiss R, Refetoff S. A thyroid hormone analog with reduced dependence on the monocarboxylate transporter 8 for tissue transport. Endocrinology. 2009;150:4450-8 pubmed publisher
    Mutations of the thyroid hormone (TH) cell membrane transporter MCT8, on chromosome-X, produce severe mental and neurological impairment in men. We generated a Mct8-deficient mouse (Mct8KO) manifesting the human thyroid phenotype...
  5. Friesema E, Ganguly S, Abdalla A, Manning Fox J, Halestrap A, Visser T. Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem. 2003;278:40128-35 pubmed
    ..This transporter belongs to the monocarboxylate transporter (MCT) family and is most homologous with MCT8 (SLC16A2). Therefore, we cloned rat MCT8 and tested it for thyroid hormone transport in Xenopus laevis oocytes...
  6. Trajkovic M, Visser T, Mittag J, Horn S, Lukas J, Darras V, et al. Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8. J Clin Invest. 2007;117:627-35 pubmed
    In humans, inactivating mutations in the gene of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8; SLC16A2) lead to severe forms of psychomotor retardation combined with imbalanced thyroid hormone serum levels...
  7. Abe S, Namba N, Abe M, Fujiwara M, Aikawa T, Kogo M, et al. Monocarboxylate transporter 10 functions as a thyroid hormone transporter in chondrocytes. Endocrinology. 2012;153:4049-58 pubmed publisher
    ..Thus, untreated congenital hypothyroidism is marked by severe short stature. The monocarboxylate transporter 8 (MCT8) is a highly specific transporter for thyroid hormone...
  8. Heuer H, Visser T. Minireview: Pathophysiological importance of thyroid hormone transporters. Endocrinology. 2009;150:1078-83 pubmed publisher
    ..Recently, several active and specific thyroid hormone transporters have been identified, including monocarboxylate transporter 8 (MCT8), MCT10, and organic anion transporting polypeptide 1C1 (OATP1C1)...
  9. Ferrara A, Liao X, Gil Ibáñez P, Marcinkowski T, Bernal J, Weiss R, et al. Changes in thyroid status during perinatal development of MCT8-deficient male mice. Endocrinology. 2013;154:2533-41 pubmed publisher
    Patients with the monocarboxylate transporter 8 (MCT8) deficiency syndrome present with a severe psychomotor retardation and abnormal serum thyroid hormone (TH) levels, consisting of high T(3) and low T(4) and rT(3)...

More Information

Publications47

  1. Liao X, Di Cosmo C, Dumitrescu A, Hernandez A, van Sande J, St Germain D, et al. Distinct roles of deiodinases on the phenotype of Mct8 defect: a comparison of eight different mouse genotypes. Endocrinology. 2011;152:1180-91 pubmed publisher
    Mice deficient in the thyroid hormone (TH) transporter Mct8 (Mct8KO) have increased 5'-deiodination and impaired TH secretion and excretion...
  2. Morte B, Ceballos A, Diez D, Grijota Martinez C, Dumitrescu A, Di Cosmo C, et al. Thyroid hormone-regulated mouse cerebral cortex genes are differentially dependent on the source of the hormone: a study in monocarboxylate transporter-8- and deiodinase-2-deficient mice. Endocrinology. 2010;151:2381-7 pubmed publisher
    ..T(3) in the brain depends on T(3) transport through the blood-brain barrier, mediated in part by the monocarboxylate transporter 8 (Mct8/MCT8) and the activity of type 2 deiodinase (D2) generating T(3) from T(4)...
  3. Trajkovic Arsic M, Visser T, Darras V, Friesema E, Schlott B, Mittag J, et al. Consequences of monocarboxylate transporter 8 deficiency for renal transport and metabolism of thyroid hormones in mice. Endocrinology. 2010;151:802-9 pubmed publisher
    ..phenotype characterized by high-serum T(3) and low-serum T(4) levels is also found in mice mutants deficient in MCT8 although the cause of these abnormalities is still unknown...
  4. Ceballos A, Belinchon M, Sanchez Mendoza E, Grijota Martinez C, Dumitrescu A, Refetoff S, et al. Importance of monocarboxylate transporter 8 for the blood-brain barrier-dependent availability of 3,5,3'-triiodo-L-thyronine. Endocrinology. 2009;150:2491-6 pubmed publisher
    Mutations of the gene expressing plasma membrane transporter for thyroid hormones MCT8 (SLC16A2) in humans lead to altered thyroid hormone levels and a severe neurodevelopmental disorder...
  5. Roberts L, Woodford K, Zhou M, Black D, Haggerty J, Tate E, et al. Expression of the thyroid hormone transporters monocarboxylate transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the blood-brain barrier. Endocrinology. 2008;149:6251-61 pubmed publisher
    ..was highlighted by the discovery that inactivating mutations in the human monocarboxylate transporter-8 (MCT8) (SLC16A2) cause severe psychomotor retardation due to thyroid hormone deficiency in the central nervous system...
  6. Muller J, Mayerl S, Visser T, Darras V, Boelen A, Frappart L, et al. Tissue-specific alterations in thyroid hormone homeostasis in combined Mct10 and Mct8 deficiency. Endocrinology. 2014;155:315-25 pubmed publisher
    ..transport of thyroid hormone (TH) and shows an overlapping expression with the well-established TH transporter Mct8. Because Mct8 deficiency is associated with distinct tissue-specific alterations in TH transport and metabolism, we ..
  7. Di Cosmo C, Liao X, Ye H, Ferrara A, Weiss R, Refetoff S, et al. Mct8-deficient mice have increased energy expenditure and reduced fat mass that is abrogated by normalization of serum T3 levels. Endocrinology. 2013;154:4885-95 pubmed publisher
    Children with monocarboxylate transporter 8 (MCT8) deficiency lose weight, even when adequately nourished...
  8. Capelo L, Beber E, Fonseca T, Gouveia C. The monocarboxylate transporter 8 and L-type amino acid transporters 1 and 2 are expressed in mouse skeletons and in osteoblastic MC3T3-E1 cells. Thyroid. 2009;19:171-80 pubmed publisher
    ..co-transporting polypeptide (NTCP), the L-type amino acid transporter 1 (LAT1) and 2 (LAT2), and the monocarboxylate transporter 8 (MCT8)...
  9. Braun D, Kinne A, Bräuer A, Sapin R, Klein M, Köhrle J, et al. Developmental and cell type-specific expression of thyroid hormone transporters in the mouse brain and in primary brain cells. Glia. 2011;59:463-71 pubmed publisher
    ..One of these, monocarboxylate transporter 8 (MCT8) is mutated in Allan-Herndon-Dudley syndrome, a severe mental retardation associated with ..
  10. Dumitrescu A, Liao X, Weiss R, Millen K, Refetoff S. Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice. Endocrinology. 2006;147:4036-43 pubmed
    Mutations of the X-linked thyroid hormone (TH) transporter (monocarboxylate transporter, MCT8) produce in humans unusual abnormalities of thyroid function characterized by high serum T3 and low T4 and rT3...
  11. Becker H, Mohebbi N, Perna A, Ganapathy V, Capasso G, Wagner C. Localization of members of MCT monocarboxylate transporter family Slc16 in the kidney and regulation during metabolic acidosis. Am J Physiol Renal Physiol. 2010;299:F141-54 pubmed publisher
    ..Here, we investigated selected members of the MCT family in the mouse kidney. MCT1, MCT2, MCT7, and MCT8 localized to basolateral membranes of the epithelial cells lining the nephron...
  12. Domènech Estévez E, Baloui H, Repond C, Rosafio K, Médard J, Tricaud N, et al. Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination. J Neurosci. 2015;35:4151-6 pubmed publisher
    ..These data indicate that lactate homeostasis participates in the regulation of the SC myelination program and reveal that similar to CNS, PNS axon-glial metabolic interactions are most likely mediated by MCTs. ..
  13. Ohba K, Leow M, Singh B, Sinha R, Lesmana R, Liao X, et al. Desensitization and Incomplete Recovery of Hepatic Target Genes After Chronic Thyroid Hormone Treatment and Withdrawal in Male Adult Mice. Endocrinology. 2016;157:1660-72 pubmed publisher
    ..Our findings may be a potential reason for discordance between clinical symptoms and serum TH levels observed in these conditions. ..
  14. Vasilopoulou E, Loubiere L, Heuer H, Trajkovic Arsic M, Darras V, Visser T, et al. Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice. PLoS ONE. 2013;8:e65402 pubmed publisher
    b>Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay...
  15. Puchades M, Sogn C, Maehlen J, Bergersen L, Gundersen V. Unaltered lactate and glucose transporter levels in the MPTP mouse model of Parkinson's disease. J Parkinsons Dis. 2013;3:371-85 pubmed publisher
    ..This is in contrast to findings in other neurodegenerative disease, such as mesial temporal lobe epilepsy, where there are large alterations in MCT levels. ..
  16. Kogai T, Liu Y, Richter L, Mody K, Kagechika H, Brent G. Retinoic acid induces expression of the thyroid hormone transporter, monocarboxylate transporter 8 (Mct8). J Biol Chem. 2010;285:27279-88 pubmed publisher
    ..Mct8 (monocarboxylate transporter 8), expressed predominantly in the brain and placenta, mediates thyroid hormone uptake from the ..
  17. Wittmann G, Szabon J, Mohácsik P, Nouriel S, Gereben B, Fekete C, et al. Parallel regulation of thyroid hormone transporters OATP1c1 and MCT8 during and after endotoxemia at the blood-brain barrier of male rodents. Endocrinology. 2015;156:1552-64 pubmed publisher
    ..important for brain TH homeostasis, organic anion-transporting polypeptide 1c1 (OATP1c1), and monocarboxylate transporter 8 (MCT8)...
  18. Selmi Ruby S, Bouazza L, Obregon M, Conscience A, Flamant F, Samarut J, et al. The targeted inactivation of TR? gene in thyroid follicular cells suggests a new mechanism of regulation of thyroid hormone production. Endocrinology. 2014;155:635-46 pubmed publisher
    ..deiodinases D1 and D2 were reduced as well as the expression levels of genes encoding monocarboxylate transporters (Mct8 and Mct10)...
  19. Smith V, Read M, Turnell A, Sharma N, Lewy G, Fong J, et al. PTTG-binding factor (PBF) is a novel regulator of the thyroid hormone transporter MCT8. Endocrinology. 2012;153:3526-36 pubmed publisher
    ..symporter (NIS) delivers iodide from the bloodstream into the thyroid, and after TH biosynthesis, monocarboxylate transporter 8 (MCT8) mediates TH secretion from the thyroid gland...
  20. Leitch V, Di Cosmo C, Liao X, O Boy S, Galliford T, Evans H, et al. An Essential Physiological Role for MCT8 in Bone in Male Mice. Endocrinology. 2017;158:3055-3066 pubmed publisher
    ..We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone...
  21. Sharlin D, Visser T, Forrest D. Developmental and cell-specific expression of thyroid hormone transporters in the mouse cochlea. Endocrinology. 2011;152:5053-64 pubmed publisher
    ..L-type amino acid transporter 1 localized to cochlear blood vessels and transiently to sensory hair cells. Mct8 localized to the greater epithelial ridge, tympanic border cells underlying the sensory epithelium, spiral ligament ..
  22. Martinez M, Karaczyn A, Stohn J, Donnelly W, Croteau W, Peeters R, et al. The Type 3 Deiodinase Is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis. Endocrinology. 2016;157:1276-88 pubmed publisher
    ..Similarly, genetic deficiencies in the D2 or in the monocarboxylate transporter 8 partially rescue the abnormalities in testis size and gonadal axis gene expression featured in the ..
  23. Johannes J, Jayarama Naidu R, Meyer F, Wirth E, Schweizer U, Schomburg L, et al. Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8. Endocrinology. 2016;157:1694-701 pubmed publisher
    ..a screening of 13 chemicals, suspicious for TH receptor interaction, to test their potential effects on THTT in MCT8-overexpressing MDCK1-cells...
  24. Rodrigues T, Ceballos A, Grijota Martínez C, Nuñez B, Refetoff S, Cerdán S, et al. Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8). PLoS ONE. 2013;8:e74621 pubmed publisher
    Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment...
  25. Horn S, Kersseboom S, Mayerl S, Muller J, Groba C, Trajkovic Arsic M, et al. Tetrac can replace thyroid hormone during brain development in mouse mutants deficient in the thyroid hormone transporter mct8. Endocrinology. 2013;154:968-79 pubmed publisher
    The monocarboxylate transporter 8 (MCT8) plays a critical role in mediating the uptake of thyroid hormones (THs) into the brain...
  26. Fagman H, Amendola E, Parrillo L, Zoppoli P, Marotta P, Scarfò M, et al. Gene expression profiling at early organogenesis reveals both common and diverse mechanisms in foregut patterning. Dev Biol. 2011;359:163-75 pubmed publisher
    ..As an initial step in this direction we describe a regulatory pathway involving the anti-apoptotic gene Bcl2 that controls cell survival in early thyroid development. ..
  27. Núñez B, Martinez de Mena R, Obregon M, Font Llitjós M, Nunes V, Palacin M, et al. Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation. PLoS ONE. 2014;9:e96915 pubmed publisher
    ..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 ..
  28. Boussouar F, Mauduit C, Tabone E, Pellerin L, Magistretti P, Benahmed M. Developmental and hormonal regulation of the monocarboxylate transporter 2 (MCT2) expression in the mouse germ cells. Biol Reprod. 2003;69:1069-78 pubmed
  29. Stohn J, Martinez M, Matoin K, Morte B, Bernal J, Galton V, et al. MCT8 Deficiency in Male Mice Mitigates the Phenotypic Abnormalities Associated With the Absence of a Functional Type 3 Deiodinase. Endocrinology. 2016;157:3266-77 pubmed publisher
    ..Here we examined how these phenotypes are affected by a deficiency in the monocarboxylate transporter 8 (MCT8), which is a major contributor to the transport of the active thyroid hormone, T3, into the cell...
  30. Chureau C, Prissette M, Bourdet A, Barbe V, Cattolico L, Jones L, et al. Comparative sequence analysis of the X-inactivation center region in mouse, human, and bovine. Genome Res. 2002;12:894-908 pubmed
  31. Kobayashi S, Totoki Y, Soma M, Matsumoto K, Fujihara Y, Toyoda A, et al. Identification of an imprinted gene cluster in the X-inactivation center. PLoS ONE. 2013;8:e71222 pubmed publisher
    ..This finding may help in understanding the molecular mechanisms regulating imprinted X-chromosome inactivation during early mammalian development. ..
  32. Ferrara A, Liao X, Ye H, Weiss R, Dumitrescu A, Refetoff S. The Thyroid Hormone Analog DITPA Ameliorates Metabolic Parameters of Male Mice With Mct8 Deficiency. Endocrinology. 2015;156:3889-94 pubmed publisher
    Mutations in the gene encoding the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), cause mental retardation in humans associated with a specific thyroid hormone phenotype manifesting high serum T3 and low T4 and ..
  33. Sugiura M, Nagaoka M, Yabuuchi H, Akaike T. Overexpression of MCT8 enhances the differentiation of ES cells into neural progenitors. Biochem Biophys Res Commun. 2007;360:741-5 pubmed
    ..Among the 27 types of SLC family transporters, MCT8 expression was coincident with that of neural stem cell markers, and the overexpression of MCT8 accelerated the ..
  34. Heuer H. The importance of thyroid hormone transporters for brain development and function. Best Pract Res Clin Endocrinol Metab. 2007;21:265-76 pubmed
    ..The monocarboxylate transporter 8 (MCT8) was recently characterized as a very specific thyroid hormone transporter...
  35. Ferrara A, Liao X, Gil Ibáñez P, Bernal J, Weiss R, Dumitrescu A, et al. Placenta passage of the thyroid hormone analog DITPA to male wild-type and Mct8-deficient mice. Endocrinology. 2014;155:4088-93 pubmed publisher
    b>Monocarboxylate transporter 8 (MCT8) deficiency causes severe X-linked intellectual and neuropsychological impairment associated with abnormal thyroid function tests (TFTs) producing thyroid hormone (TH) deprivation in brain and excess ..
  36. Debrand E, Heard E, Avner P. Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene. Genomics. 1998;48:296-303 pubmed
    ..We have cloned and mapped the mouse homolog of the human XPCT (X-linked PEST-containing transporter) gene, which encodes a putative transmembrane transporter...
  37. Sun S, Fukue Y, Nolen L, Sadreyev R, Lee J. Characterization of Xpr (Xpct) reveals instability but no effects on X-chromosome pairing or Xist expression. Transcription. 2010;1:46-56 pubmed publisher
    ..A recent study suggested a new pairing element (Xpr), located ~200 kb upstream of Xist, in the Xpct region. Xpr is proposed to induce pairing and activate Xist expression...
  38. Mayerl S, Muller J, Bauer R, Richert S, Kassmann C, Darras V, et al. Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. J Clin Invest. 2014;124:1987-99 pubmed
    ..abnormal thyroid hormone (TH) parameters, is linked to mutations in the TH-specific monocarboxylate transporter MCT8. In mice, deletion of Mct8 (Mct8 KO) faithfully replicates AHDS-associated endocrine abnormalities; however, unlike ..