Monocarboxylate transporter 8: Difference between revisions

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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
{{Infobox_gene}}
'''Monocarboxylate transporter 8''' ('''MCT8''') is an active transporter [[protein]] that in humans is encoded by the ''SLC16A2'' [[gene]].<ref name="pmid7981683">{{cite journal | vauthors = Lafrenière RG, Carrel L, Willard HF | title = A novel transmembrane transporter encoded by the XPCT gene in Xq13.2 | journal = Human Molecular Genetics | volume = 3 | issue = 7 | pages = 1133–9 | date = Jul 1994 | pmid = 7981683 | pmc = | doi = 10.1093/hmg/3.7.1133 }}</ref><ref name="pmid12871948">{{cite journal | vauthors = 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 = The Journal of Biological Chemistry | volume = 278 | issue = 41 | pages = 40128–35 | date = Oct 2003 | pmid = 12871948 | pmc = | doi = 10.1074/jbc.M300909200 }}</ref><ref name="pmid15889350">{{cite journal | vauthors = 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 = American Journal of Human Genetics | volume = 77 | issue = 1 | pages = 41–53 | date = Jul 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>
'''Monocarboxylate transporter 8''' ('''MCT8''') is an active transporter [[protein]] that in humans is encoded by the ''SLC16A2'' [[gene]].<ref name="pmid7981683">{{cite journal | vauthors = Lafrenière RG, Carrel L, Willard HF | title = A novel transmembrane transporter encoded by the XPCT gene in Xq13.2 | journal = Human Molecular Genetics | volume = 3 | issue = 7 | pages = 1133–9 | date = Jul 1994 | pmid = 7981683 | doi = 10.1093/hmg/3.7.1133 }}</ref><ref name="pmid12871948">{{cite journal | vauthors = 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 = The Journal of Biological Chemistry | volume = 278 | issue = 41 | pages = 40128–35 | date = Oct 2003 | pmid = 12871948 | doi = 10.1074/jbc.M300909200 | doi-access = free }}</ref><ref name="pmid15889350">{{cite journal | vauthors = 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 = American Journal of Human Genetics | volume = 77 | issue = 1 | pages = 41–53 | date = Jul 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 = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6567}}</ref>


== Function ==
== Function ==
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== Clinical significance ==
== Clinical significance ==


A genetic disorder (discovered in 2003<ref name="pmid12871948"/> and 2004<ref name="pmid14661163">{{cite journal | vauthors = 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 = American Journal of Human Genetics | volume = 74 | issue = 1 | pages = 168–75 | date = Jan 2004 | pmid = 14661163 | pmc = 1181904 | doi = 10.1086/380999 }}</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 [[leukoencephalopathy]].<ref name="pmid21415082">{{cite journal | vauthors = 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 = Journal of Medical Genetics | volume = 48 | issue = 9 | pages = 606–9 | date = Sep 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 | vauthors = 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 = Annals of Neurology | volume = 65 | issue = 1 | pages = 114–8 | date = Jan 2009 | pmid = 19194886 | doi = 10.1002/ana.21579 }}</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"/> and 2004<ref name="pmid14661163">{{cite journal | vauthors = 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 = American Journal of Human Genetics | volume = 74 | issue = 1 | pages = 168–75 | date = Jan 2004 | pmid = 14661163 | pmc = 1181904 | doi = 10.1086/380999 }}</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 [[leukoencephalopathy]].<ref name="pmid21415082">{{cite journal | vauthors = 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 = Journal of Medical Genetics | volume = 48 | issue = 9 | pages = 606–9 | date = Sep 2011 | pmid = 21415082 | doi = 10.1136/jmg.2010.083535 | s2cid = 1157351 }}</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 | vauthors = 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 = Annals of Neurology | volume = 65 | issue = 1 | pages = 114–8 | date = Jan 2009 | pmid = 19194886 | doi = 10.1002/ana.21579 | s2cid = 27740314 }}</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 ==
⚫
=== Zebrafish ===
⚫
A knockout [[zebrafish]] line was generated in 2014 using the [[Zinc finger nuclease|zinc-finger nuclease (ZFN)]]-mediated targeted gene editing system.<ref>{{cite journal | vauthors = Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L | title = Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation | journal = PLOS Genetics | volume = 10 | issue = 9 | pages = e1004615 | date = Sep 2014 | pmid = 25255244 | pmc = 4177677 | doi = 10.1371/journal.pgen.1004615 | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L | title = Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation | journal = PLOS Genetics | volume = 10 | issue = 9 | pages = e1004615 | date = Sep 2014 | pmc = 4177677 | doi = 10.1371/journal.pgen.1004615 | pmid = 25255244 | doi-access = free }}</ref>


⚫
=== ''Xenopus'' ===
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
Expression of ''mct8'' has been characterised in ''[[Xenopus laevis]]''<ref>{{Cite journal|last1=Mughal|first1=Bilal B.|last2=Leemans|first2=Michelle|last3=Lima de Souza|first3=Elaine C.|last4=le Mevel|first4=Sébastien|last5=Spirhanzlova|first5=Petra|last6=Visser|first6=Theo J.|last7=Fini|first7=Jean-Baptiste|last8=Demeneix|first8=Barbara A.|date=2017-08-01|title=Functional Characterization of Xenopus Thyroid Hormone Transporters mct8 and oatp1c1|journal=Endocrinology|volume=158|issue=8|pages=2694–2705|doi=10.1210/en.2017-00108|issn=1945-7170|pmid=28591769|doi-access=free}}</ref> and ''[[Xenopus tropicalis]]''.<ref>{{Cite journal|last1=Connors|first1=Kristin A.|last2=Korte|first2=Joseph J.|last3=Anderson|first3=Grant W.|last4=Degitz|first4=Sigmund J.|date=2010-08-01|title=Characterization of thyroid hormone transporter expression during tissue-specific metamorphic events in Xenopus tropicalis|journal=General and Comparative Endocrinology|volume=168|issue=1|pages=149–159|doi=10.1016/j.ygcen.2010.04.015|issn=1095-6840|pmid=20417208}}</ref>
|+ ''Slc16a2'' knockout mouse phenotype
|-
! Characteristic!! Phenotype

|-
| [[Homozygote]] viability || bgcolor="#488ED3"|Normal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#C40000"|Abnormal<ref name="Glucose tolerance test">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKY/glucose-tolerance-ip/ |title=Glucose tolerance test data for Slc16a2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#C40000"|Abnormal<ref name="Clinical chemistry">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKY/plasma-chemistry/ |title=Clinical chemistry data for Slc16a2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#C40000"|Abnormal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKY/salmonella-challenge/ |title=''Salmonella'' infection data for Slc16a2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKY/citrobacter-challenge/ |title=''Citrobacter'' infection data for Slc16a2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages = 925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}

⚫
=== Mice ===
A conditional [[knockout mouse]] line, called ''Slc16a2<sup>tm1a(KOMP)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Slc16a2 |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4364794 |title=Mouse Genome Informatics}}</ref> 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.<ref name="pmid21677750">{{cite journal | vauthors = 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 | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref>

Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biology | volume = 12 | issue = 6 | pages = 224 | year = 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref> Twenty one tests were carried out on [[mutant]] mice and three significant abnormalities were observed.<ref name="mgp_reference" /> 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.<ref name="mgp_reference" />

⚫
=== Zebrafish ===
⚫
A knockout [[zebrafish]] line was generated in 2014 using the [[Zinc finger nuclease|zinc-finger nuclease (ZFN)]]-mediated targeted gene editing system.<ref>{{cite journal | vauthors = Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L | title = Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation | journal = PLoS Genetics | volume = 10 | issue = 9 | pages = e1004615 | date = Sep 2014 | pmid = 25255244 | pmc = 4177677 | doi = 10.1371/journal.pgen.1004615 | url = http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004615 }}</ref> 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.<ref>{{cite journal | vauthors = Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L | title = Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation | journal = PLoS Genetics | volume = 10 | issue = 9 | pages = e1004615 | date = Sep 2014 | pmc = 4177677 | doi = 10.1371/journal.pgen.1004615 | pmid = 25255244 }}</ref>


== See also ==
== See also ==
Line 79: Line 26:
== Further reading ==
== Further reading ==
{{refbegin|33em}}
{{refbegin|33em}}
* {{cite journal | vauthors = Halestrap AP, Meredith D | title = The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond | journal = Pflügers Archiv | volume = 447 | issue = 5 | pages = 619–28 | date = Feb 2004 | pmid = 12739169 | doi = 10.1007/s00424-003-1067-2 }}
* {{cite journal | vauthors = Halestrap AP, Meredith D | title = The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond | journal = Pflügers Archiv | volume = 447 | issue = 5 | pages = 619–28 | date = Feb 2004 | pmid = 12739169 | doi = 10.1007/s00424-003-1067-2 | s2cid = 15498611 }}
* {{cite journal | vauthors = Friesema EC, Jansen J, Heuer H, Trajkovic M, Bauer K, Visser TJ | title = Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8 | journal = Nature Clinical Practice. Endocrinology & Metabolism | volume = 2 | issue = 9 | pages = 512–23 | date = Sep 2006 | pmid = 16957765 | doi = 10.1038/ncpendmet0262 }}
* {{cite journal | vauthors = Friesema EC, Jansen J, Heuer H, Trajkovic M, Bauer K, Visser TJ | title = Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8 | journal = Nature Clinical Practice Endocrinology & Metabolism | volume = 2 | issue = 9 | pages = 512–23 | date = Sep 2006 | pmid = 16957765 | doi = 10.1038/ncpendmet0262 | s2cid = 25232696 }}
* {{cite journal | vauthors = Grüters A | title = Thyroid hormone transporter defects | journal = Endocrine Development | volume = 10 | issue = | pages = 118–26 | year = 2007 | pmid = 17684393 | doi = 10.1159/0000106823 }}
* {{cite journal | vauthors = Grüters A | title = Thyroid hormone transporter defects | journal = Endocrine Development | volume = 10 | pages = 118–26 | year = 2007 | pmid = 17684393 | doi = 10.1159/000106823 | isbn = 978-3-8055-8296-4 }}
* {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Analytical Biochemistry | volume = 236 | issue = 1 | pages = 107–13 | date = Apr 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
* {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Analytical Biochemistry | volume = 236 | issue = 1 | pages = 107–13 | date = Apr 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
* {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-scale concatenation cDNA sequencing | journal = Genome Research | volume = 7 | issue = 4 | pages = 353–8 | date = Apr 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
* {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-scale concatenation cDNA sequencing | journal = Genome Research | volume = 7 | issue = 4 | pages = 353–8 | date = Apr 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
* {{cite journal | vauthors = Price NT, Jackson VN, Halestrap AP | title = Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past | journal = The Biochemical Journal | volume = 329 ( Pt 2) | issue = 2 | pages = 321–8 | date = Jan 1998 | pmid = 9425115 | pmc = 1219047 | doi = }}
* {{cite journal | vauthors = Price NT, Jackson VN, Halestrap AP | title = Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past | journal = The Biochemical Journal | volume = 329 | issue = 2 | pages = 321–8 | date = Jan 1998 | pmid = 9425115 | pmc = 1219047 | doi = 10.1042/bj3290321}}
* {{cite journal | vauthors = Debrand E, Heard E, Avner P | title = Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene | journal = Genomics | volume = 48 | issue = 3 | pages = 296–303 | date = Mar 1998 | pmid = 9545634 | doi = 10.1006/geno.1997.5173 }}
* {{cite journal | vauthors = Debrand E, Heard E, Avner P | title = Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene | journal = Genomics | volume = 48 | issue = 3 | pages = 296–303 | date = Mar 1998 | pmid = 9545634 | doi = 10.1006/geno.1997.5173 }}
* {{cite journal | vauthors = 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 = American Journal of Human Genetics | volume = 74 | issue = 1 | pages = 168–75 | date = Jan 2004 | pmid = 14661163 | pmc = 1181904 | doi = 10.1086/380999 }}
* {{cite journal | vauthors = 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 = American Journal of Human Genetics | volume = 74 | issue = 1 | pages = 168–75 | date = Jan 2004 | pmid = 14661163 | pmc = 1181904 | doi = 10.1086/380999 }}
* {{cite journal | vauthors = Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MH, Kuiper GG, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ | title = Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation | journal = Lancet | volume = 364 | issue = 9443 | pages = 1435–7 | year = 2004 | pmid = 15488219 | doi = 10.1016/S0140-6736(04)17226-7 }}
* {{cite journal | vauthors = Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MH, Kuiper GG, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ | title = Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation | journal = Lancet | volume = 364 | issue = 9443 | pages = 1435–7 | year = 2004 | pmid = 15488219 | doi = 10.1016/S0140-6736(04)17226-7 | s2cid = 37520843 }}
* {{cite journal | vauthors = Heuer H, Maier MK, Iden S, Mittag J, Friesema EC, Visser TJ, Bauer K | title = The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations | journal = Endocrinology | volume = 146 | issue = 4 | pages = 1701–6 | date = Apr 2005 | pmid = 15661862 | doi = 10.1210/en.2004-1179 }}
* {{cite journal | vauthors = Heuer H, Maier MK, Iden S, Mittag J, Friesema EC, Visser TJ, Bauer K | title = The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations | journal = Endocrinology | volume = 146 | issue = 4 | pages = 1701–6 | date = Apr 2005 | pmid = 15661862 | doi = 10.1210/en.2004-1179 | doi-access = free }}
* {{cite journal | vauthors = Brockmann K, Dumitrescu AM, Best TT, Hanefeld F, Refetoff S | title = X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene | journal = Journal of Neurology | volume = 252 | issue = 6 | pages = 663–6 | date = Jun 2005 | pmid = 15834651 | doi = 10.1007/s00415-005-0713-3 }}
* {{cite journal | vauthors = Brockmann K, Dumitrescu AM, Best TT, Hanefeld F, Refetoff S | title = X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene | journal = Journal of Neurology | volume = 252 | issue = 6 | pages = 663–6 | date = Jun 2005 | pmid = 15834651 | doi = 10.1007/s00415-005-0713-3 | s2cid = 31994320 }}
* {{cite journal | vauthors = Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH | title = Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism | journal = Molecular Endocrinology | volume = 20 | issue = 11 | pages = 2761–72 | date = Nov 2006 | pmid = 16887882 | doi = 10.1210/me.2005-0256 }}
* {{cite journal | vauthors = Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH | title = Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism | journal = Molecular Endocrinology | volume = 20 | issue = 11 | pages = 2761–72 | date = Nov 2006 | pmid = 16887882 | doi = 10.1210/me.2005-0256 | doi-access = free }}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 }}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | s2cid = 7827573 | doi-access = free }}
* {{cite journal | vauthors = Jansen J, Friesema EC, Kester MH, Milici C, Reeser M, Grüters A, Barrett TG, Mancilla EE, Svensson J, Wemeau JL, Busi da Silva Canalli MH, Lundgren J, McEntagart ME, Hopper N, Arts WF, Visser TJ | title = Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 92 | issue = 6 | pages = 2378–81 | date = Jun 2007 | pmid = 17356046 | doi = 10.1210/jc.2006-2570 }}
* {{cite journal | vauthors = Jansen J, Friesema EC, Kester MH, Milici C, Reeser M, Grüters A, Barrett TG, Mancilla EE, Svensson J, Wemeau JL, Busi da Silva Canalli MH, Lundgren J, McEntagart ME, Hopper N, Arts WF, Visser TJ | title = Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 92 | issue = 6 | pages = 2378–81 | date = Jun 2007 | pmid = 17356046 | doi = 10.1210/jc.2006-2570 | doi-access = free }}
{{refend}}
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[[Category:Solute carrier family]]
[[Category:Solute carrier family]]
[[Category:Genes mutated in mice]]
[[Category:Genes mutated in mice]]
[[Category: Thyroid hormone transporters]]

Latest revision as of 19:23, 31 December 2023

SLC16A2
Identifiers
AliasesSLC16A2, DXS128, DXS128E, MCT 7, MCT 8, MCT7, MCT8, MRX22, XPCT, AHDS, solute carrier family 16 member 2
External IDsOMIM: 300095; MGI: 1203732; HomoloGene: 39495; GeneCards: SLC16A2; OMA:SLC16A2 - orthologs
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: 102.74 – 102.87 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[edit]

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

Clinical significance[edit]

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[edit]

Zebrafish[edit]

A knockout zebrafish line was generated in 2014 using the zinc-finger nuclease (ZFN)-mediated targeted gene editing system.[12] 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.[13]

Xenopus[edit]

Expression of mct8 has been characterised in Xenopus laevis[14] and Xenopus tropicalis.[15]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000147100 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033965 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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. doi:10.1093/hmg/3.7.1133. PMID 7981683.
  6. ^ 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". The Journal of Biological Chemistry. 278 (41): 40128–35. doi:10.1074/jbc.M300909200. PMID 12871948.
  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. doi:10.1086/431313. PMC 1226193. PMID 15889350.
  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. doi:10.1086/380999. PMC 1181904. PMID 14661163.
  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. doi:10.1136/jmg.2010.083535. PMID 21415082. S2CID 1157351.
  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. doi:10.1002/ana.21579. PMID 19194886. S2CID 27740314.
  12. ^ 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. doi:10.1371/journal.pgen.1004615. PMC 4177677. PMID 25255244.
  13. ^ 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. doi:10.1371/journal.pgen.1004615. PMC 4177677. PMID 25255244.
  14. ^ Mughal, Bilal B.; Leemans, Michelle; Lima de Souza, Elaine C.; le Mevel, Sébastien; Spirhanzlova, Petra; Visser, Theo J.; Fini, Jean-Baptiste; Demeneix, Barbara A. (2017-08-01). "Functional Characterization of Xenopus Thyroid Hormone Transporters mct8 and oatp1c1". Endocrinology. 158 (8): 2694–2705. doi:10.1210/en.2017-00108. ISSN 1945-7170. PMID 28591769.
  15. ^ Connors, Kristin A.; Korte, Joseph J.; Anderson, Grant W.; Degitz, Sigmund J. (2010-08-01). "Characterization of thyroid hormone transporter expression during tissue-specific metamorphic events in Xenopus tropicalis". General and Comparative Endocrinology. 168 (1): 149–159. doi:10.1016/j.ygcen.2010.04.015. ISSN 1095-6840. PMID 20417208.

Further reading[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Monocarboxylate_transporter_8&oldid=1192862022"