Interleukin-23 receptor
Interleukin 23 receptor is a type I cytokine receptor. IL23R is its human gene.[1]
Function
The protein encoded by this gene is a subunit of the receptor for IL23A/IL23. This protein pairs with the receptor molecule IL12RB1/IL12Rbeta1, and both are required for IL23A signaling. This protein associates constitutively with Janus kinase 2 (JAK2), and also binds to transcription activator STAT3 in a ligand-dependent manner.[1]
Clinical significance
Three variants in the IL23R gene have been shown to protect against Crohn's disease and ulcerative colitis.[2][3][4]
Model organisms
Model organisms have been used in the study of IL23R function. A conditional knockout mouse line called Il23rtm2a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[5] Male and female animals underwent a standardized phenotypic screen[6] to determine the effects of deletion.[7][8][9][10] Additional screens performed: - In-depth immunological phenotyping[11]
| Characteristic | Phenotype |
|---|---|
| All data available at.[6][11] | |
| Peripheral blood leukocytes 6 Weeks | Normal |
| Insulin | Normal |
| Haematology 6 Weeks | Normal |
| Homozygous viability at P14 | Normal |
| Homozygous Fertility | Normal |
| Body weight | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology 16 Weeks | Normal |
| Peripheral blood leukocytes 16 Weeks | Normal |
| Heart weight | Normal |
| Salmonella infection | Normal |
| Cytotoxic T Cell Function | Normal |
| Spleen Immunophenotyping | Normal |
| Mesenteric Lymph Node Immunophenotyping | Normal |
| Bone Marrow Immunophenotyping | Normal |
| Epidermal Immune Composition | Normal |
References
- 1 2 "Entrez Gene: IL23R interleukin 23 receptor".
- ↑ Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. (Dec 2006). "A genome-wide association study identifies IL23R as an inflammatory bowel disease gene". Science 314 (5804): 1461–3. doi:10.1126/science.1135245. PMID 17068223.
- ↑ Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, et al. (Nov 2011). "Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease". Nature Genetics 43 (11): 1066–73. doi:10.1038/ng.952. PMC 3378381. PMID 21983784.
- ↑ Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, et al. (Jan 2011). "Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease". Nature Genetics 43 (1): 43–7. doi:10.1038/ng.733. PMID 21151126.
- ↑ 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.
- 1 2 "International Mouse Phenotyping Consortium".
- ↑ 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 (Jun 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 (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
- 1 2 "Infection and Immunity Immunophenotyping (3i) Consortium".
Further reading
- Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW (Jun 2002). "A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R". Journal of Immunology 168 (11): 5699–708. doi:10.4049/jimmunol.168.11.5699. PMID 12023369.
- Zhang XY, Zhang HJ, Zhang Y, Fu YJ, He J, Zhu LP, Wang SH, Liu L (Jan 2006). "Identification and expression analysis of alternatively spliced isoforms of human interleukin-23 receptor gene in normal lymphoid cells and selected tumor cells". Immunogenetics 57 (12): 934–43. doi:10.1007/s00251-005-0067-0. PMID 16372191.
- Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (Dec 2006). "A genome-wide association study identifies IL23R as an inflammatory bowel disease gene". Science 314 (5804): 1461–3. doi:10.1126/science.1135245. PMID 17068223.
- Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB (Feb 2007). "A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes". American Journal of Human Genetics 80 (2): 273–90. doi:10.1086/511051. PMC 1785338. PMID 17236132.
- Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, Dutridge D, Wahbeh G, Silber G, Bahar R, Mengesha E, Targan SR, Taylor KD, Rotter JI (May 2007). "IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease". Inflammatory Bowel Diseases 13 (5): 511–5. doi:10.1002/ibd.20126. PMC 2169293. PMID 17309073.
- Tremelling M, Cummings F, Fisher SA, Mansfield J, Gwilliam R, Keniry A, Nimmo ER, Drummond H, Onnie CM, Prescott NJ, Sanderson J, Bredin F, Berzuini C, Forbes A, Lewis CM, Cardon L, Deloukas P, Jewell D, Mathew CG, Parkes M, Satsangi J (May 2007). "IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease". Gastroenterology 132 (5): 1657–64. doi:10.1053/j.gastro.2007.02.051. PMC 2696256. PMID 17484863.
- Cummings JR, Ahmad T, Geremia A, Beckly J, Cooney R, Hancock L, Pathan S, Guo C, Cardon LR, Jewell DP (Sep 2007). "Contribution of the novel inflammatory bowel disease gene IL23R to disease susceptibility and phenotype". Inflammatory Bowel Diseases 13 (9): 1063–8. doi:10.1002/ibd.20180. PMID 17508420.
- Yamazaki K, Onouchi Y, Takazoe M, Kubo M, Nakamura Y, Hata A (2007). "Association analysis of genetic variants in IL23R, ATG16L1 and 5p13.1 loci with Crohn's disease in Japanese patients". Journal of Human Genetics 52 (7): 575–83. doi:10.1007/s10038-007-0156-z. PMID 17534574.
- Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, Frackelton EC, Otieno FG, Kanterakis S, Shaner JL, Smith RM, Eckert AW, Robinson LJ, Onyiah CC, Abrams DJ, Chiavacci RM, Skraban R, Devoto M, Grant SF, Hakonarson H (Aug 2007). "Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease". Clinical Gastroenterology and Hepatology 5 (8): 972–6. doi:10.1016/j.cgh.2007.04.024. PMID 17618837.
- Sánchez E, Rueda B, Callejas JL, Sabio JM, Ortego-Centeno N, Jimenez-Alonso J, López-Nevot MA, Martín J (Sep 2007). "Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus". Tissue Antigens 70 (3): 233–7. doi:10.1111/j.1399-0039.2007.00881.x. PMID 17661912.
- Orozco G, Rueda B, Robledo G, García A, Martín J (Aug 2007). "Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort". Human Immunology 68 (8): 681–4. doi:10.1016/j.humimm.2007.05.008. PMID 17678723.
- Oliver J, Rueda B, López-Nevot MA, Gómez-García M, Martín J (Aug 2007). "Replication of an association between IL23R gene polymorphism with inflammatory bowel disease". Clinical Gastroenterology and Hepatology 5 (8): 977–81, 981.e1–2. doi:10.1016/j.cgh.2007.05.002. PMID 17678845.
- Raelson JV, Little RD, Ruether A, Fournier H, Paquin B, Van Eerdewegh P, Bradley WE, Croteau P, Nguyen-Huu Q, Segal J, Debrus S, Allard R, Rosenstiel P, Franke A, Jacobs G, Nikolaus S, Vidal JM, Szego P, Laplante N, Clark HF, Paulussen RJ, Hooper JW, Keith TP, Belouchi A, Schreiber S (Sep 2007). "Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci". Proceedings of the National Academy of Sciences of the United States of America 104 (37): 14747–52. doi:10.1073/pnas.0706645104. PMC 1965486. PMID 17804789.
- Borgiani P, Perricone C, Ciccacci C, Romano S, Novelli G, Biancone L, Petruzziello C, Pallone F (Sep 2007). "Interleukin-23R Arg381Gln is associated with susceptibility to Crohn's disease but not with phenotype in an Italian population". Gastroenterology 133 (3): 1049–51; author reply 1051–2. doi:10.1053/j.gastro.2007.07.013. PMID 17854611.
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