RGD Reference Report - Lack of DNA mismatch repair protein MSH6 in the rat results in hereditary non-polyposis colorectal cancer-like tumorigenesis. - Rat Genome Database

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

Authors: Van Boxtel, R  Toonen, P  Van Roekel, H  Verheul, M  Smits, BM  Korving, J  De Bruin, A  Cuppen, E 
Citation: van Boxtel R, etal., Carcinogenesis. 2008 Apr 15;.
RGD ID: 2292505
Pubmed: PMID:18417481   (View Abstract at PubMed)
DOI: DOI:10.1093/carcin/bgn094   (Journal Full-text)

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/deletion loops and responding to genotoxic agents. Here, we describe the functional characterization of a novel rat mutant model in which the mismatch repair gene Msh6 has been genetically inactivated by N-ethyl-N-nitrosourea (ENU)-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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mismatch repair  IMP 2292505 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased tumor incidence  IMP 2292505; 2292505; 2292505 RGD 
premature death  IMP 2292505; 2292505; 2292505 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Msh6  (mutS homolog 6)
Msh6m1Hubr  (mutS homolog 6; ENU induced mutant 1, Hubr)

Genes (Mus musculus)
Msh6  (mutS homolog 6)

Genes (Homo sapiens)
MSH6  (mutS homolog 6)

Strains
WI- Msh6m1Hubr  (NA)


Additional Information