Lack of DNA mismatch repair protein MSH6 in the rat results in hereditary non-polyposis colorectal cancer-like tumorigenesis.

TY - JOUR

T1 - Lack of DNA mismatch repair protein MSH6 in the rat results in hereditary non-polyposis colorectal cancer-like tumorigenesis.

AU - van Boxtel, R.

AU - Toonen, P.W.

AU - van Roekel, H.S.

AU - Verheul, M.

AU - Smits, B.M.

AU - Korving, J.

AU - de Bruin, A.

AU - Cuppen, E.

N1 - Reporting year: 2008

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1093/carcin/bgn094

DO - 10.1093/carcin/bgn094

M3 - Article

SN - 0143-3334

VL - 29

SP - 1290

EP - 1297

JO - Carcinogenesis

JF - Carcinogenesis

IS - 6

ER -