Monocarboxylate transporter 8: Difference between revisions

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{{PBB|geneid=6567}}
{{PBB|geneid=6567}}
'''Monocarboxylate transporter 8 (MCT8)''' is a [[protein]] that in humans is encoded by the ''SLC16A2'' [[gene]].<ref name="pmid7981683">{{cite journal | author = Lafreniere RG, Carrel L, Willard HF | title = A novel transmembrane transporter encoded by the XPCT gene in Xq13.2 | journal = Hum Mol Genet | volume = 3 | issue = 7 | pages = 1133–9 | year = 1995 | month = Jan | pmid = 7981683 | pmc = | doi =10.1093/hmg/3.7.1133 }}</ref><ref name="pmid12871948">{{cite journal | author = Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ | title = Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter | journal = J Biol Chem | volume = 278 | issue = 41 | pages = 40128–35 | year = 2003 | month = Oct | pmid = 12871948 | pmc = | doi = 10.1074/jbc.M300909200 }}</ref><ref name="pmid15889350">{{cite journal | author = 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 | title = Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene | journal = Am J Hum Genet | volume = 77 | issue = 1 | pages = 41–53 | year = 2005 | month = Jun | pmid = 15889350 | pmc = 1226193 | doi = 10.1086/431313 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC16A2 solute carrier family 16, member 2 (monocarboxylic acid transporter 8)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6567| accessdate = }}</ref>
'''Monocarboxylate transporter 8 (MCT8)''' is a [[protein]] that in humans is encoded by the ''SLC16A2'' [[gene]].<ref name="pmid7981683">{{cite journal | author = Lafreniere RG, Carrel L, Willard HF | title = A novel transmembrane transporter encoded by the XPCT gene in Xq13.2 | journal = Hum Mol Genet | volume = 3 | issue = 7 | pages = 1133–9 |date=Jan 1995 | pmid = 7981683 | pmc = | doi =10.1093/hmg/3.7.1133 }}</ref><ref name="pmid12871948">{{cite journal | author = Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ | title = Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter | journal = J Biol Chem | volume = 278 | issue = 41 | pages = 40128–35 |date=Oct 2003 | pmid = 12871948 | pmc = | doi = 10.1074/jbc.M300909200 }}</ref><ref name="pmid15889350">{{cite journal | author = 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 | title = Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene | journal = Am J Hum Genet | volume = 77 | issue = 1 | pages = 41–53 |date=Jun 2005 | pmid = 15889350 | pmc = 1226193 | doi = 10.1086/431313 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC16A2 solute carrier family 16, member 2 (monocarboxylic acid transporter 8)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6567| accessdate = }}</ref>


== Function ==
== Function ==
Line 8: Line 8:
== Clinical significance ==
== Clinical significance ==


A genetic disorder (discovered in 2003<ref name="pmid12871948">{{cite journal | author = Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ | title = Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter | journal = J. Biol. Chem. | volume = 278 | issue = 41 | pages = 40128–35 | year = 2003 | month = October | pmid = 12871948 | doi = 10.1074/jbc.M300909200 | url = | issn = }}</ref> and 2004<ref name="pmid14661163">{{cite journal | author = Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S | title = A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene | journal = Am. J. Hum. Genet. | volume = 74 | issue = 1 | pages = 168–75 | year = 2004 | month = January | pmid = 14661163 | pmc = 1181904 | doi = 10.1086/380999 | url = | issn = }}</ref>) 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 [[hypotonia|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]].<ref name="pmid21415082">{{cite journal | author = Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N | title = Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing | journal = J. Med. Genet. | volume = 48 | issue = 9 | pages = 606–9 | year = 2011 | month = September | pmid = 21415082 | doi = 10.1136/jmg.2010.083535 }}</ref> Some of the symptoms for this disorder as are follows: normal to slightly elevated [[thyroid-stimulating hormone|TSH]], elevated T<sub>3</sub> and reduced T<sub>4</sub> (ratio of T<sub>3</sub>/T<sub>4</sub> 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<ref name="pmid19194886">{{cite journal | author = 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 | title = Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects | journal = Ann. Neurol. | volume = 65 | issue = 1 | pages = 114–8 | year = 2009 | month = January | pmid = 19194886 | doi = 10.1002/ana.21579 | url = | issn = }}</ref>), possibly with decreased mitochondrial enzyme activities, possibly with fluctuating [[lactic acid| 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/T<sub>4</sub>/T<sub>3</sub> thyroid test.
A genetic disorder (discovered in 2003<ref name="pmid12871948">{{cite journal | author = Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ | title = Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter | journal = J. Biol. Chem. | volume = 278 | issue = 41 | pages = 40128–35 |date=October 2003 | pmid = 12871948 | doi = 10.1074/jbc.M300909200 | url = | issn = }}</ref> and 2004<ref name="pmid14661163">{{cite journal | author = Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S | title = A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene | journal = Am. J. Hum. Genet. | volume = 74 | issue = 1 | pages = 168–75 |date=January 2004 | pmid = 14661163 | pmc = 1181904 | doi = 10.1086/380999 | url = | issn = }}</ref>) 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 [[hypotonia|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]].<ref name="pmid21415082">{{cite journal | author = Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N | title = Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing | journal = J. Med. Genet. | volume = 48 | issue = 9 | pages = 606–9 |date=September 2011 | pmid = 21415082 | doi = 10.1136/jmg.2010.083535 }}</ref> Some of the symptoms for this disorder as are follows: normal to slightly elevated [[thyroid-stimulating hormone|TSH]], elevated T<sub>3</sub> and reduced T<sub>4</sub> (ratio of T<sub>3</sub>/T<sub>4</sub> 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<ref name="pmid19194886">{{cite journal | author = 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 | title = Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects | journal = Ann. Neurol. | volume = 65 | issue = 1 | pages = 114–8 |date=January 2009 | pmid = 19194886 | doi = 10.1002/ana.21579 | url = | issn = }}</ref>), possibly with decreased mitochondrial enzyme activities, possibly with fluctuating [[lactic acid| 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/T<sub>4</sub>/T<sub>3</sub> thyroid test.


==Model organisms==
==Model organisms==

Revision as of 03:19, 30 January 2014

Template:PBB 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ a b c 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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) Cite error: The named reference "pmid12871948" was defined multiple times with different content (see the help page).
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. ^ a b c d 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. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21677750, please use {{cite journal}} with |pmid=21677750 instead.
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)

Further reading

Template:PBB Further reading

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