SLC16A2

From Wikipedia, the free encyclopedia
Solute carrier family 16, member 2 (thyroid hormone transporter)
Identifiers
SymbolsSLC16A2; AHDS; DXS128; DXS128E; MCT 7; MCT 8; MCT7; MCT8; MRX22; XPCT
External IDsOMIM: 300095 MGI: 1203732 HomoloGene: 39495 GeneCards: SLC16A2 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez656720502
EnsemblENSG00000147100ENSMUSG00000033965
UniProtP36021O70324
RefSeq (mRNA)NM_006517NM_009197
RefSeq (protein)NP_006508NP_033223
Location (UCSC)Chr X:
73.64 – 73.75 Mb		Chr X:
103.7 – 103.82 Mb
PubMed search
This box:

Monocarboxylate transporter 8 (MCT8) is a protein that in humans is encoded by the SLC16A2 gene.[1][2][3][4]

Function

MCT8 transports a variety of iodo-thyronines including the thyroid hormones T3 and T4.[2]

Clinical significance

A genetic disorder (discovered in 2003[2] and 2004[5]) 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 leucoencephalopathy.[6] 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[7]), 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

Model organisms have been used in the study of SLC16A2 function. A conditional knockout mouse line, called Slc16a2tm1a(KOMP)Wtsi[14][15] 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.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty one tests were carried out on mutant mice and three significant abnormalities were observed.[12] 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.[12]

See also

References

  1. ↑ Lafreniere RG, Carrel L, Willard HF (Jan 1995). "A novel transmembrane transporter encoded by the XPCT gene in Xq13.2". Hum Mol Genet 3 (7): 1133–9. doi:10.1093/hmg/3.7.1133. PMID 7981683. 
  2. ↑ 2.0 2.1 2.2 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". J Biol Chem 278 (41): 40128–35. doi:10.1074/jbc.M300909200. PMID 12871948. 
  3. ↑ 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 (Jun 2005). "Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene". Am J Hum Genet 77 (1): 41–53. doi:10.1086/431313. PMC 1226193. PMID 15889350. 
  4. ↑ "Entrez Gene: SLC16A2 solute carrier family 16, member 2 (monocarboxylic acid transporter 8)". 
  5. ↑ Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S (January 2004). "A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene". Am. J. Hum. Genet. 74 (1): 168–75. doi:10.1086/380999. PMC 1181904. PMID 14661163. 
  6. ↑ Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N (September 2011). "Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing". J. Med. Genet. 48 (9): 606–9. doi:10.1136/jmg.2010.083535. PMID 21415082. 
  7. ↑ 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 (January 2009). "Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects". Ann. Neurol. 65 (1): 114–8. doi:10.1002/ana.21579. PMID 19194886. 
  8. ↑ "Glucose tolerance test data for Slc16a2". Wellcome Trust Sanger Institute. 
  9. ↑ "Clinical chemistry data for Slc16a2". Wellcome Trust Sanger Institute. 
  10. ↑ "Salmonella infection data for Slc16a2". Wellcome Trust Sanger Institute. 
  11. ↑ "Citrobacter infection data for Slc16a2". Wellcome Trust Sanger Institute. 
  12. ↑ 12.0 12.1 12.2 12.3 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. 
  13. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  14. ↑ "International Knockout Mouse Consortium". 
  15. ↑ "Mouse Genome Informatics". 
  16. ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750. 
  17. ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  18. ↑ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  19. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 

Further reading

This article is issued from Wikipedia. The text is available under the Creative Commons Attribution/Share Alike; additional terms may apply for the media files.