Back to Search
Start Over
Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene.
- Source :
-
The EMBO journal [EMBO J] 1999 Nov 01; Vol. 18 (21), pp. 5931-42. - Publication Year :
- 1999
-
Abstract
- Ectopic expression of certain Wnt genes in mouse mammary tissue is tumorigenic, and mutations that stabilize beta-catenin are found in various human cancers including colorectal cancer. To determine the role of stabilized beta-catenin in intestinal tumorigenesis in mice, we constructed by embryonic stem (ES) cell-mediated homologous recombination, a mutant beta-catenin allele whose exon 3 was sandwiched by loxP sequences. When the germline heterozygotes were crossed with mice expressing Cre recombinase in the intestines, the serines and threonine encoded by exon 3 and to be phosphorylated by glycogen synthase kinase 3beta (GSK3beta) were deleted in the offspring intestines, which caused adenomatous intestinal polyps resembling those in Apc(Delta716) knockout mice. Some nascent microadenomas were also found in the colon. These results present experimental genetic evidence that activation of the Wnt signaling pathway can cause intestinal and colonic tumors.
- Subjects :
- Animals
Colonic Neoplasms genetics
Disease Models, Animal
Gene Targeting methods
Genes, Dominant
Integrases genetics
Intestinal Neoplasms genetics
Intestinal Polyps pathology
Mice
Mice, Knockout
Mutation
Proto-Oncogene Proteins genetics
Recombination, Genetic
Signal Transduction genetics
Stem Cells
Wnt Proteins
beta Catenin
Cytoskeletal Proteins genetics
Intestinal Polyps genetics
Trans-Activators
Viral Proteins
Zebrafish Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 18
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 10545105
- Full Text :
- https://doi.org/10.1093/emboj/18.21.5931