Monocarboxylate transporter 8

SLC16A2
Identifiers
AliasesSLC16A2, DXS128, DXS128E, MCT 7, MCT 8, MCT7, MCT8, MRX22, XPCT, AHDS, solute carrier family 16 member 2
External IDsMGI: 1203732 HomoloGene: 39495 GeneCards: SLC16A2
Gene location (Human)
Chr.X chromosome (human)[1]
BandNo data availableStart74,421,461 bp[1]
End74,533,917 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

6567

20502

Ensembl

ENSG00000147100

ENSMUSG00000033965

UniProt

P36021

O70324

RefSeq (mRNA)

NM_006517

NM_009197

RefSeq (protein)

NP_006508

NP_033223

Location (UCSC)Chr X: 74.42 – 74.53 MbChr X: 103.7 – 103.82 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Monocarboxylate transporter 8 (MCT8) is an active transporter protein that in humans is encoded by the SLC16A2 gene.[5][6][7][8]

Function

MCT8 actively transports a variety of iodo-thyronines including the thyroid hormones T3 and T4.[6]

Clinical significance

A genetic disorder (discovered in 2003[6] and 2004[9]) is caused by mutation in the transporter of thyroid hormone, MCT8, also known as SLC16A2, is believed to be account for a significant fraction of the undiagnosed neurological disorders (usually resulting in hypotonic/floppy infants with delayed milestones). This genetic defect was known as Allan–Herndon–Dudley syndrome (since 1944) without knowing its actual cause. It has been shown mutated in cases of X-linked leukoencephalopathy.[10] Some of the symptoms for this disorder as are follows: normal to slightly elevated TSH, elevated T3 and reduced T4 (ratio of T3/T4 is about double its normal value). Normal looking at birth and for the first few years, hypotonic (floppy), in particular difficulty to hold the head, possibly difficulty to thrive, possibly with delayed myelination (if so, some cases are reported with an MRI pattern similar to Pelizaeus–Merzbacher disease, known as PMD[11]), possibly with decreased mitochondrial enzyme activities, possibly with fluctuating lactate level. Patients have an alert face, a limited IQ, patients may never talk/walk, 50% need feeding tube, patients have a normal life span. This disease can be ruled out with a simple TSH/T4/T3 thyroid test.

Model organisms

Mice

A conditional knockout mouse line, called Slc16a2tm1a(KOMP)Wtsi[18][19] was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[20][21][22]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[16][23] Twenty one tests were carried out on mutant mice and three significant abnormalities were observed.[16] Female homozygote mutants had decreased circulating glucose levels. Male hemizygous mutants had an increased susceptibility to bacterial infection. Both sexes had various abnormal plasma chemistry parameters.[16]

Zebrafish

A knockout zebrafish line was generated in 2014 using the zinc-finger nuclease (ZFN)-mediated targeted gene editing system.[24] Similar to human patients, the zebrafish larvae exhibited neurological and behavioral deficiencies. They demonstrated reduced locomotor activity, altered myelin-related genes and neuron-specific deficiencies in circuit formation.[25]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000147100 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000033965 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ Lafrenière RG, Carrel L, Willard HF (Jul 1994). "A novel transmembrane transporter encoded by the XPCT gene in Xq13.2". Human Molecular Genetics. 3 (7): 1133–9. PMID 7981683. doi:10.1093/hmg/3.7.1133.
  6. 1 2 3 Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ (Oct 2003). "Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter". The Journal of Biological Chemistry. 278 (41): 40128–35. PMID 12871948. doi:10.1074/jbc.M300909200.
  7. ↑ Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG, Ward J, Sanabria J, Marsa S, Lewis JA, Echeverri R, Lubs HA, Voeller K, Simensen RJ, Stevenson RE (Jul 2005). "Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene". American Journal of Human Genetics. 77 (1): 41–53. PMC 1226193 Freely accessible. PMID 15889350. doi:10.1086/431313.
  8. ↑ "Entrez Gene: SLC16A2 solute carrier family 16, member 2 (monocarboxylic acid transporter 8)".
  9. ↑ Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S (Jan 2004). "A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene". American Journal of Human Genetics. 74 (1): 168–75. PMC 1181904 Freely accessible. PMID 14661163. doi:10.1086/380999.
  10. ↑ Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N (Sep 2011). "Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing". Journal of Medical Genetics. 48 (9): 606–9. PMID 21415082. doi:10.1136/jmg.2010.083535.
  11. ↑ Vaurs-Barrière C, Deville M, Sarret C, Giraud G, Des Portes V, Prats-Viñas JM, De Michele G, Dan B, Brady AF, Boespflug-Tanguy O, Touraine R (Jan 2009). "Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects". Annals of Neurology. 65 (1): 114–8. PMID 19194886. doi:10.1002/ana.21579.
  12. ↑ "Glucose tolerance test data for Slc16a2". Wellcome Trust Sanger Institute.
  13. ↑ "Clinical chemistry data for Slc16a2". Wellcome Trust Sanger Institute.
  14. ↑ "Salmonella infection data for Slc16a2". Wellcome Trust Sanger Institute.
  15. ↑ "Citrobacter infection data for Slc16a2". Wellcome Trust Sanger Institute.
  16. 1 2 3 4 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  17. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  18. ↑ "International Knockout Mouse Consortium".
  19. ↑ "Mouse Genome Informatics".
  20. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. PMC 3572410 Freely accessible. PMID 21677750. doi:10.1038/nature10163.
  21. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. PMID 21677718. doi:10.1038/474262a.
  22. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. PMID 17218247. doi:10.1016/j.cell.2006.12.018.
  23. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. PMC 3218837 Freely accessible. PMID 21722353. doi:10.1186/gb-2011-12-6-224.
  24. ↑ Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L (Sep 2014). "Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation". PLoS Genetics. 10 (9): e1004615. PMC 4177677 Freely accessible. PMID 25255244. doi:10.1371/journal.pgen.1004615.
  25. ↑ Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L (Sep 2014). "Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation". PLoS Genetics. 10 (9): e1004615. PMC 4177677 Freely accessible. PMID 25255244. doi:10.1371/journal.pgen.1004615.

Further reading

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