TCF7L1
transcription factor 7-like 1 (T-cell specific, HMG-box), also known as TCF7L1, is a human gene.[1]
This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence.[1]
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 | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Skin Histopathology | Normal |
| Salmonella infection | Normal[2] |
| Citrobacter infection | Normal[3] |
| All tests and analysis from[4][5] |
Model organisms have been used in the study of TCF7L1 function. A conditional knockout mouse line, called Tcf7l1tm1a(EUCOMM)Wtsi[6][7] 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.[8][9][10]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][11] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed.[4] Few homozygous mutant embryos were identified during gestation, and those that did survive had a severe craniofacial defect. None survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.[4]
References
- ↑ 1.0 1.1 "Entrez Gene: transcription factor 7-like 1 (T-cell specific, HMG-box)". Retrieved 2011-08-30.
- ↑ "Salmonella infection data for Tcf7l1". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Tcf7l1". Wellcome Trust Sanger Institute.
- ↑ 4.0 4.1 4.2 4.3 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".
- ↑ "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.
- ↑ 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
- Castrop J, van Norren K, Clevers H (1992). "A gene family of HMG-box transcription factors with homology to TCF-1.". Nucleic Acids Res. 20 (3): 611. doi:10.1093/nar/20.3.611. PMC 310434. PMID 1741298.
- Sagara N, Katoh M (2000). "Mitomycin C resistance induced by TCF-3 overexpression in gastric cancer cell line MKN28 is associated with DT-diaphorase down-regulation.". Cancer Res. 60 (21): 5959–62. PMID 11085512.
- Kim TW, Kim HJ, Lee C, et al. (2008). "Identification of replicative senescence-associated genes in human umbilical vein endothelial cells by an annealing control primer system.". Exp. Gerontol. 43 (4): 286–95. doi:10.1016/j.exger.2007.12.010. PMID 18258400.
- Rose JE, Behm FM, Drgon T, et al. "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.". Mol. Med. 16 (7-8): 247–53. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614.
- Katoh M (2007). "Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis.". Stem Cell Rev 3 (1): 30–8. doi:10.1007/s12015-007-0006-6. PMID 17873379.
- Filleur S, Hirsch J, Wille A, et al. (2009). "INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling.". Cancer Cell Int. 9: 28. doi:10.1186/1475-2867-9-28. PMC 2779787. PMID 19906297.
- Balaz P, Plaschke J, Kr?ger S, et al. (2010). "TCF-3, 4 protein expression correlates with beta-catenin expression in MSS and MSI-H colorectal cancer from HNPCC patients but not in sporadic colorectal cancers.". Int J Colorectal Dis 25 (8): 931–9. doi:10.1007/s00384-010-0959-9. PMID 20532534.
- Salins P, Shawesh S, He Y, et al. (2007). "Lovastatin protects human neurons against Abeta-induced toxicity and causes activation of beta-catenin-TCF/LEF signaling.". Neurosci. Lett. 412 (3): 211–6. doi:10.1016/j.neulet.2006.07.045. PMID 17234346.
- Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4.". Nature 434 (7034): 724–31. doi:10.1038/nature03466. PMID 15815621.
- Halatsch ME, L?w S, Mursch K, et al. (2009). "Candidate genes for sensitivity and resistance of human glioblastoma multiforme cell lines to erlotinib. Laboratory investigation.". J. Neurosurg. 111 (2): 211–8. doi:10.3171/2008.9.JNS08551. PMID 19301967.
- 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.
- Barker N, Huls G, Korinek V, Clevers H (1999). "Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium.". Am. J. Pathol. 154 (1): 29–35. doi:10.1016/S0002-9440(10)65247-9. PMC 1853446. PMID 9916915.
- Velasco J, Zarrabeitia MT, Prieto JR, et al. (2010). "Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study.". Osteoporos Int 21 (1): 109–18. doi:10.1007/s00198-009-0931-0. PMID 19373426.
- Strausberg RL, Feingold EA, Grouse LH,et al. (2002). "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.
- Graham TA, Weaver C, Mao F, et al. (2000). "Crystal structure of a beta-catenin/Tcf complex.". Cell 103 (6): 885–96. doi:10.1016/S0092-8674(00)00192-6. PMID 11136974.
- Lukas J, Mazna P, Valenta T, et al. (2009). "Dazap2 modulates transcription driven by the Wnt effector TCF-4.". Nucleic Acids Res. 37 (9): 3007–20. doi:10.1093/nar/gkp179. PMC 2685103. PMID 19304756.
- Ollila HM, Soronen P, Silander K, et al. (2009). "Findings from bipolar disorder genome-wide association studies replicate in a Finnish bipolar family-cohort.". Mol. Psychiatry 14 (4): 351–3. doi:10.1038/mp.2008.122. PMC 2694406. PMID 19308021.
- Pollheimer J, Loregger T, Sonderegger S,et al. (2006). "Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast.". Am. J. Pathol. 168 (4): 1134–47. doi:10.2353/ajpath.2006.050686. PMC 1606554. PMID 16565489.
- Brantjes H, Roose J, van De Wetering M, Clevers H (2001). "All Tcf HMG box transcription factors interact with Groucho-related co-repressors.". Nucleic Acids Res. 29 (7): 1410–9. doi:10.1093/nar/29.7.1410. PMC 31284. PMID 11266540.