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- Title
Lack of DNA mismatch repair protein MSH6 in the rat results in hereditary non-polyposis colorectal cancer-like tumorigenesis.
- Authors
Ruben van Boxtel; Pim W. Toonen; Henk S. van Roekel; Mark Verheul; Bart M. G. Smits; Jeroen Korving; Alain de Bruin; Edwin Cuppen
- Abstract
To understand genetic instability in relation to tumorigenesis, experimental animal models have proven very useful. The DNA mismatch repair (MMR) machinery safeguards genomic integrity by repairing mismatches, insertion or deletion loops and responding to genotoxic agents. Here, we describe the functional characterization of a novel rat mutant model in which the MMR gene Msh6 has been genetically inactivated by N-ethyl-N-nitrosourea-driven target-selected mutagenesis. This model shows a robust mutator phenotype that is reflected by microsatellite instability and an increased germ line point mutation frequency. Consequently, these rats develop a spectrum of tumors with a high similarity to atypical hereditary non-polyposis colorectal cancer in humans. The MSH6 knockout rat complements existing models for studying genetic instable tumorigenesis as it provides experimental opportunities that are not available or suboptimal in current models.
- Subjects
GENETICS of colon cancer; DNA repair; POLYPS; CARCINOGENESIS; MUTAGENESIS; MICROSATELLITE repeats; LABORATORY rats
- Publication
Carcinogenesis, 2008, Vol 29, Issue 6, p1290
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgn094