Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin - PubMed (original) (raw)
Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin
Heather Ireland et al. Gastroenterology. 2004 May.
Abstract
Background & aims: A system for introducing specific gene mutations into the epithelia of the adult murine gastrointestinal tract by the transcriptional regulation of Cre recombinase is presented and applied to delete beta-catenin, a central mediator of Wnt signaling, within the small intestine (SI).
Methods: In a transgenic line (Ahcre), cre expression is inducible from a cytochrome P450 promoter element that is transcriptionally up-regulated in response to lipophilic xenobiotics such as beta-napthoflavone.
Results: Recombination at a lacZ reporter locus showed extensive expression of beta-galactosidase in liver, intestine, pancreas, gallbladder, esophagus, and stomach in response to beta-napthoflavone treatment. Expression patterns were stable in renewing epithelia for at least 6 months, implying that long-lived stem cells undergo recombination. Analysis of the intestinal epithelium showed dose responsiveness in the extent of recombination and that villus and crypt populations could be targeted differentially by varying the route of administration of beta-napthoflavone. The use of this system to delete beta-catenin in the SI caused crypt ablation, increased apoptosis, depleted numbers of goblet cells, and detachment of villus absorptive cells from the villus core as intact sheets.
Conclusions: The Ahcre model provides a simple route for introducing specific gene mutations into many of the epithelia of the gastrointestinal tract of the mouse. It has been used here to show that beta-catenin is required for the maintenance of intestinal cell proliferation and is implicated in goblet cell differentiation and enterocyte-matrix attachment.
Similar articles
- Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine.
Andreu P, Colnot S, Godard C, Gad S, Chafey P, Niwa-Kawakita M, Laurent-Puig P, Kahn A, Robine S, Perret C, Romagnolo B. Andreu P, et al. Development. 2005 Mar;132(6):1443-51. doi: 10.1242/dev.01700. Epub 2005 Feb 16. Development. 2005. PMID: 15716339 - Phases of canonical Wnt signaling during the development of mouse intestinal epithelium.
Kim BM, Mao J, Taketo MM, Shivdasani RA. Kim BM, et al. Gastroenterology. 2007 Aug;133(2):529-38. doi: 10.1053/j.gastro.2007.04.072. Epub 2007 May 3. Gastroenterology. 2007. PMID: 17681174 - Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
Bierie B, Nozawa M, Renou JP, Shillingford JM, Morgan F, Oka T, Taketo MM, Cardiff RD, Miyoshi K, Wagner KU, Robinson GW, Hennighausen L. Bierie B, et al. Oncogene. 2003 Jun 19;22(25):3875-87. doi: 10.1038/sj.onc.1206426. Oncogene. 2003. PMID: 12813461 - Wnt, stem cells and cancer in the intestine.
Pinto D, Clevers H. Pinto D, et al. Biol Cell. 2005 Mar;97(3):185-96. doi: 10.1042/BC20040094. Biol Cell. 2005. PMID: 15715524 Review.
Cited by
- METTL3 restricts RIPK1-dependent cell death via the ATF3-cFLIP axis in the intestinal epithelium.
Huang M, Wang X, Zhang M, Liu Y, Chen YG. Huang M, et al. Cell Regen. 2024 Aug 2;13(1):14. doi: 10.1186/s13619-024-00197-8. Cell Regen. 2024. PMID: 39093347 Free PMC article. - Protein arginine methyltransferase 1 is required for the maintenance of adult small intestinal and colonic epithelial cell homeostasis.
Peng Z, Bao L, Shi B, Shi YB. Peng Z, et al. Int J Biol Sci. 2024 Jan 1;20(2):554-568. doi: 10.7150/ijbs.89958. eCollection 2024. Int J Biol Sci. 2024. PMID: 38169732 Free PMC article. - The mechanism of intestinal stem cells differentiation after ischemia-reperfusion injury in a rat model.
Ben-Shahar Y, Vasserman V, Pollak Y, Kremer K, Sukhotnik I. Ben-Shahar Y, et al. Pediatr Surg Int. 2023 Dec 18;40(1):23. doi: 10.1007/s00383-023-05610-y. Pediatr Surg Int. 2023. PMID: 38108924 - Cross talk between Paneth and tuft cells drives dysbiosis and inflammation in the gut mucosa.
Coutry N, Nguyen J, Soualhi S, Gerbe F, Meslier V, Dardalhon V, Almeida M, Quinquis B, Thirion F, Herbert F, Gasmi I, Lamrani A, Giordano A, Cesses P, Garnier L, Thirard S, Greuet D, Cazevieille C, Bernex F, Bressuire C, Winton D, Matsumoto I, Blottière HM, Taylor N, Jay P. Coutry N, et al. Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2219431120. doi: 10.1073/pnas.2219431120. Epub 2023 Jun 12. Proc Natl Acad Sci U S A. 2023. PMID: 37307458 Free PMC article. - The intestine: A highly dynamic microenvironment for IgA plasma cells.
Pracht K, Wittner J, Kagerer F, Jäck HM, Schuh W. Pracht K, et al. Front Immunol. 2023 Feb 16;14:1114348. doi: 10.3389/fimmu.2023.1114348. eCollection 2023. Front Immunol. 2023. PMID: 36875083 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases