GFM1
Elongation factor G 1, mitochondrial is a protein that in humans is encoded by the GFM1 gene. It is an EF-G homolog.[4][5][6]
Eukaryotes contain two protein translational systems, one in the cytoplasm and one in the mitochondria. Mitochondrial translation is crucial for maintaining mitochondrial function and mutations in this system lead to a breakdown in the respiratory chain-oxidative phosphorylation system and to impaired maintenance of mitochondrial DNA. This gene encodes one of the mitochondrial translation elongation factors. Its role in the regulation of normal mitochondrial function and in different disease states attributed to mitochondrial dysfunction is not known.[6]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Recessive lethal study | Abnormal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal[7] |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal[8] |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Eye Histopathology | Normal |
| Salmonella infection | Normal[9] |
| Citrobacter infection | Normal[10] |
| All tests and analysis from[11][12] |
Model organisms have been used in the study of GFM1 function. A conditional knockout mouse line, called Gfm1tm1a(EUCOMM)Wtsi[13][14] 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.[15][16][17]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[11][18] Twenty four tests were carried out on mutant mice and three significant abnormalities were observed.[11] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and decreased circulating amylase levels were observed in male animals.[11]
References
- GRCh38: Ensembl release 89: ENSG00000168827 - 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.
- Gao J, Yu L, Zhang P, Jiang J, Chen J, Peng J, Wei Y, Zhao S (May 2001). "Cloning and characterization of human and mouse mitochondrial elongation factor G, GFM and Gfm, and mapping of GFM to human chromosome 3q25.1-q26.2". Genomics. 74 (1): 109–14. doi:10.1006/geno.2001.6536. PMID 11374907.
- Hammarsund M, Wilson W, Corcoran M, Merup M, Einhorn S, Grander D, Sangfelt O (Dec 2001). "Identification and characterization of two novel human mitochondrial elongation factor genes, hEFG2 and hEFG1, phylogenetically conserved through evolution". Hum Genet. 109 (5): 542–50. doi:10.1007/s00439-001-0610-5. PMID 11735030. S2CID 24508386.
- "Entrez Gene: GFM1 G elongation factor, mitochondrial 1".
- "Clinical chemistry data for Gfm1". Wellcome Trust Sanger Institute.
- "Peripheral blood lymphocytes data for Gfm1". Wellcome Trust Sanger Institute.
- "Salmonella infection data for Gfm1". Wellcome Trust Sanger Institute.
- "Citrobacter infection data for Gfm1". 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. S2CID 85911512.
- Mouse Resources Portal, Wellcome Trust Sanger Institute.
- "International Knockout Mouse Consortium".
- "Mouse Genome Informatics".
- 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.
- 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. S2CID 18872015.
- 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
- Bec G, Kerjan P, Zha XD, Waller JP (1990). "Valyl-tRNA synthetase from rabbit liver. I. Purification as a heterotypic complex in association with elongation factor 1". J. Biol. Chem. 264 (35): 21131–7. PMID 2556394.
- Motorin YuA; Wolfson AD; Orlovsky AF; Gladilin KL (1988). "Mammalian valyl-tRNA synthetase forms a complex with the first elongation factor". FEBS Lett. 238 (2): 262–4. doi:10.1016/0014-5793(88)80492-7. PMID 3169261. S2CID 45934458.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Bhargava K, Templeton P, Spremulli LL (2005). "Expression and characterization of isoform 1 of human mitochondrial elongation factor G". Protein Expr. Purif. 37 (2): 368–76. doi:10.1016/j.pep.2004.06.030. PMID 15358359.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Coenen MJ, Antonicka H, Ugalde C, et al. (2004). "Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency". N. Engl. J. Med. 351 (20): 2080–6. doi:10.1056/NEJMoa041878. hdl:2066/143650. PMID 15537906.
- Antonicka H, Sasarman F, Kennaway NG, Shoubridge EA (2006). "The molecular basis for tissue specificity of the oxidative phosphorylation deficiencies in patients with mutations in the mitochondrial translation factor EFG1". Hum. Mol. Genet. 15 (11): 1835–46. doi:10.1093/hmg/ddl106. PMID 16632485.
- Valente L, Tiranti V, Marsano RM, et al. (2007). "Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu". Am. J. Hum. Genet. 80 (1): 44–58. doi:10.1086/510559. PMC 1785320. PMID 17160893.