Mitochondrial 2-oxodicarboxylate carrier
Mitochondrial 2-oxodicarboxylate carrier also known as solute carrier family 25 member 21 (SLC25A21) is a protein that in humans is encoded by the SLC25A21 gene.[5]
It is a homolog of the S. cerevisiae ODC proteins, mitochondrial carriers that transport C5-C7 oxodicarboxylates across inner mitochondrial membranes. One of the species transported by ODC is 2-oxoadipate, a common intermediate in the catabolism of lysine, tryptophan, and hydroxylysine in mammals. Within mitochondria, 2-oxoadipate is converted into acetyl-CoA.[5]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Recessive lethal study | Normal |
| Fertility | Normal |
| Body weight | Abnormal[6] |
| Anxiety | Normal |
| Neurological assessment | Abnormal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Abnormal[7] |
| Indirect calorimetry | Abnormal[8] |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Abnormal |
| DEXA | Abnormal[9] |
| Radiography | Abnormal[10] |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal[11] |
| Haematology | Abnormal[12] |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Brain histopathology | Normal |
| All tests and analysis from[13][14] |
Model organisms have been used in the study of SLC25A21 function. A conditional knockout mouse line, called Slc25a21tm1a(KOMP)Wtsi[15][16] 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.[17][18][19]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][20] Twenty one tests were carried out on homozygous mutant mice and ten significant abnormalities were observed, including sub-viability at weaning, decreased body weight, absent pinna reflex, abnormal snout, skull, spine and tooth morphology, atypical indirect calorimetry, body composition and plasma chemistry data, increased mean platelet volume and moderate elevations in auditory thresholds.[13]
References
- GRCh38: Ensembl release 89: ENSG00000183032 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000035472 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Solute carrier family 25 (mitochondrial oxodicarboxylate carrier), member 21". Retrieved 2011-12-04.
- "Body weight data for Slc25a21". Wellcome Trust Sanger Institute.
- "Dysmorphology data for Slc25a21". Wellcome Trust Sanger Institute.
- "Indirect calorimetry data for Slc25a21". Wellcome Trust Sanger Institute.
- "DEXA data for Slc25a21". Wellcome Trust Sanger Institute.
- "Radiography data for Slc25a21". Wellcome Trust Sanger Institute.
- "Clinical chemistry data for Slc25a21". Wellcome Trust Sanger Institute.
- "Haematology data for Slc25a21". Wellcome Trust Sanger Institute.
- 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".
- 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 (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Further reading
- Fiermonte G, Dolce V, Palmieri L, Ventura M, Runswick MJ, Palmieri F, Walker JE (March 2001). "Identification of the human mitochondrial oxodicarboxylate carrier. Bacterial expression, reconstitution, functional characterization, tissue distribution, and chromosomal location". The Journal of Biological Chemistry. 276 (11): 8225–30. doi:10.1074/jbc.M009607200. PMID 11083877.
- Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, Bruinenberg M, Heap GA, Platteel M, Ryan AW, de Kovel C, Holmes GK, Howdle PD, Walters JR, Sanders DS, Mulder CJ, Mearin ML, Verbeek WH, Trimble V, Stevens FM, Kelleher D, Barisani D, Bardella MT, McManus R, van Heel DA, Wijmenga C (August 2009). "Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling". Gut. 58 (8): 1078–83. doi:10.1136/gut.2008.169052. PMID 19240061.
- Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, Gaunt TR, Pallas J, Lovering R, Li K, Casas JP, Sofat R, Kumari M, Rodriguez S, Johnson T, Newhouse SJ, Dominiczak A, Samani NJ, Caulfield M, Sever P, Stanton A, Shields DC, Padmanabhan S, Melander O, Hastie C, Delles C, Ebrahim S, Marmot MG, Smith GD, Lawlor DA, Munroe PB, Day IN, Kivimaki M, Whittaker J, Humphries SE, Hingorani AD (November 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121.