Biology:ASXL1
 Generic protein structure example |
Putative Polycomb group protein ASXL1 is a protein that in humans is encoded by the ASXL1 gene.[1][2]
In Drosophila, the Additional sex combs (Asx) gene encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. Although the function of the protein encoded by this gene is not known, it does show some sequence similarity to the protein encoded by the Drosophila Asx gene.[2]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Recessive lethal study | Abnormal |
| 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 | Abnormal[3] |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Skin Histopathology | Normal |
| Brain histopathology | Normal |
| MicroCT & Quantitative Faxitron | Abnormal |
| Salmonella infection | Normal[4] |
| Citrobacter infection | Normal[5] |
| All tests and analysis from[6][7] |
Model organisms have been used in the study of ASXL1 function. A conditional knockout mouse line, called Asxl1tm1a(EUCOMM)Wtsi[8][9] 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.[10][11][12]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[6][13] Twenty five tests were carried out on mutant mice and four significant abnormalities were observed.[6] Few homozygous mutant embryos were identified during gestation and those that were alive had craniofacial and eye defects, none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; decreased vertebrae number and increased bone strength was observed in these animals.[6]
References
- ↑ "A human homolog of Additional sex combs, ADDITIONAL SEX COMBS-LIKE 1, maps to chromosome 20q11". Gene 306: 115–26. Mar 2003. doi:10.1016/S0378-1119(03)00430-X. PMID 12657473.
- ↑ 2.0 2.1 "Entrez Gene: ASXL1 additional sex combs like 1 (Drosophila)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=171023.
- ↑ "Radiography data for Asxl1". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MBSP/x-ray-imaging/.
- ↑ "Salmonella infection data for Asxl1". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MBSP/salmonella-challenge/.
- ↑ "Citrobacter infection data for Asxl1". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MBSP/citrobacter-challenge/.
- ↑ 6.0 6.1 6.2 6.3 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". http://www.knockoutmouse.org/martsearch/search?query=Asxl1.
- ↑ "Mouse Genome Informatics". http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4431878.
- ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M. et al. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMID 21677750.
- ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ "A Mouse for All Reasons". Cell 128 (1): 9–13. 2007. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. 2011. doi:10.1186/gb-2011-12-6-224. PMID 21722353.
External links
- Human ASXL1 genome location and ASXL1 gene details page in the UCSC Genome Browser.
Further reading
- "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. 2003. doi:10.1093/dnares/9.3.99. PMID 12168954.
- "Genetic Analysis of the Additional Sex Combs Locus of Drosophila Melanogaster". Genetics 130 (4): 817–25. 1992. doi:10.1093/genetics/130.4.817. PMID 1349871.
- "The Additional sex combs gene of Drosophila encodes a chromatin protein that binds to shared and unique Polycomb group sites on polytene chromosomes". Development 125 (7): 1207–16. 1998. doi:10.1242/dev.125.7.1207. PMID 9477319.
- "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (1): 63–70. 1999. doi:10.1093/dnares/6.1.63. PMID 10231032.
- "The DNA sequence and comparative analysis of human chromosome 20". Nature 414 (6866): 865–71. 2002. doi:10.1038/414865a. PMID 11780052. Bibcode: 2001Natur.414..865D.
- "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
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