Disease relevance of SLC16A2

• X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene [1].
• We describe the expression of MCT8 in normal human placenta throughout gestation, and in normal third-trimester placenta compared with that associated with IUGR using quantitative reverse transcriptase PCR [2].
• By inference, local changes in thyroid hormone metabolism resulting from altered hypothalamic deiodinase or MCT8 expression may underlie the decrease in TRH mRNA reported earlier in the PVN of patients with critical illness and depression [3].
• We report a family with X-linked mental retardation that has a novel mutation in the monocarboxylate transporter 8 (MCT8) gene associated with a characteristic neurodevelopmental phenotype with early childhood hypotonia that progresses to spasticity and global developmental delays [4].

Psychiatry related information on SLC16A2

• We report a novel 1 bp deletion (c.1834delC) in the MCT8 gene in a large Brazilian family with Allan-Herndon-Dudley syndrome (AHDS), an X linked condition characterised by severe mental retardation and neurological dysfunction [5].

High impact information on SLC16A2

• These findings establish the physiological importance of MCT8 as a thyroid hormone transporter [6].
• We now report, for the first time, mutations in the monocarboxylate transporter 8 (MCT8) gene, located on the X chromosome, that encodes a 613-amino acid protein with 12 predicted transmembrane domains [6].
• MCT8 protein was not detected in nontransfected cell lines tested by immunoblotting using a polyclonal C-terminal hMCT8 antibody but was detectable in transfected cells at the expected size (61 kDa) [7].
• Our findings indicate that hMCT8 mediates plasma membrane transport of iodothyronines, thus increasing their intracellular availability [7].
• Transfection of COS1 and JEG3 cells with hMCT8 cDNA resulted in 2- to 3-fold increases in uptake of T(3) and T(4) but little or no increase in rT(3) or 3,3'-diiodothyronine (3,3'-T(2)) uptake [7].

Biological context of SLC16A2

• A BAC clone containing the marsupial SLC16A2 was mapped to the end of the long arm of the tammar X chromosome and used in RNA FISH experiments to determine whether one or both loci are transcribed in female cells [8].
• The SLC16A2 (formerly MCT8) gene is located on chromosome Xq13.2 and has recently been associated with a syndrome combining severe, X-linked, psychomotor retardation and high serum T3 levels [9].
• The coding sequence of MCT8 was analysed by PCR and direct sequencing of its six exons [10].
• MCT8 mRNA was detected in placenta from early first trimester, with a significant increase with advancing gestation (P=0.007) [2].
• Extended clinical phenotype, endocrine investigations and functional studies of a loss-of-function mutation A150V in the thyroid hormone specific transporter MCT8 [11].

Anatomical context of SLC16A2

• Together with the spatiotemporal expression pattern of MCT8 during the perinatal period, these results strongly indicate that MCT8 plays an important role for proper central nervous system development by transporting TH into neurons as its main target cells [12].
• MCT8 mRNA was detected by RT-PCR in a number of human cell lines as well as in COS1 cells but was low to undetectable in other cell lines, including JEG3 cells [7].
• By contrast, both D3 and MCT8 are expressed by neurons of the paraventricular (PVN), supraoptic, and infundibular nucleus (IFN) [13].
• 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 [14].
• A novel mutation in the monocarboxylate transporter 8 gene in a boy with putamen lesions and low free T4 levels in cerebrospinal fluid [15].

Associations of SLC16A2 with chemical compounds

• AHDS oxidation to AQDS was coupled to Fe(III) reduction to Fe(ll) in biological media consisting of trace salts and vitamins, providing estimates of bioavailability consistentwith the biogeochemical mechanisms and conditions that control Fe(III) availability to iron-reducing bacteria [16].
• The advantage of AHDS titration over existing chemical techniques is that it can be performed at normal soil pH and ionic strength, and it allows for distinction of iron(III) oxides rendered unavailable by sorption of Fe(II) or by other pH-dependent geochemical processes [16].
• Five nanograms for tricaproin (MCT-6), 10 ng for tricaprylin (MCT-8) and 15 ng for tricaprin (MCT-9) represent the GLC detection limits of MCT, while those of MCFA range from 40 to 15 ng depending on their chain length: the longer the chain length, the higher the detection limit [17].
• In addition, MCT6 and -8 were also prominently expressed in this tissue, although it is known that MCT8 does not transport aromatic amino acids or lactate [18].

Other interactions of SLC16A2

• Isolation, X location and activity of the marsupial homologue of SLC16A2, an XIST-flanking gene in eutherian mammals [8].

Analytical, diagnostic and therapeutic context of SLC16A2

• To provide a clue to the cellular function of MCT8 in brain, we studied the expression of MCT8 mRNA in the murine central nervous system by in situ hybridization histochemistry [12].
• ELISA indicated the expression of only MCT1, MCT4, and MCT8 isoforms by ARPE-19 cells [19].

References