Monocarboxylate transporter 8: Difference between revisions
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Revision as of 09:13, 12 December 2013
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
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Abnormal[8] |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal[9] |
| Haematology | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Salmonella infection | Abnormal[10] |
| Citrobacter infection | Normal[11] |
| All tests and analysis from[12][13] |
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
- ^ Lafreniere RG, Carrel L, Willard HF (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}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ (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}}: Unknown parameter|month=ignored (help)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). - ^ 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 (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}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ "Entrez Gene: SLC16A2 solute carrier family 16, member 2 (monocarboxylic acid transporter 8)".
- ^ Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S (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}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N (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}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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 (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}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ "Glucose tolerance test data for Slc16a2". Wellcome Trust Sanger Institute.
- ^ "Clinical chemistry data for Slc16a2". Wellcome Trust Sanger Institute.
- ^ "Salmonella infection data for Slc16a2". Wellcome Trust Sanger Institute.
- ^ "Citrobacter infection data for Slc16a2". Wellcome Trust Sanger Institute.
- ^ 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.
- ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ^ "International Knockout Mouse Consortium".
- ^ "Mouse Genome Informatics".
- ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21677750, please use {{cite journal}} with
|pmid=21677750instead. - ^ Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ^ 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) - ^ 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)