ArticleGastroenterology2010
An Msh2 conditional knockout mouse for studying intestinal cancer and testing anticancer agents.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 108 citations in OpenAlex.
- Trial
- Fasting-mimicking diet counteracts gut microbial dysbiosis in experimental lynch syndrome.Cancer & metabolism · 2026Article
- Mismatch repair deficiency drives malignant progression and alters the tumor immune microenvironment in glioblastoma models.The Journal of clinical investigation · 2026Article
- A common food mutagen promotes intestinal carcinogenesis by multiple mechanisms in mouse models of Lynch syndrome.NAR cancer · 2025Article
- Induced somatic mutation accumulation during skeletal muscle regeneration reduces muscle strength.Nature aging · 2025Article
- Review
- Article
- Advances in diagnostic and therapeutic applications of mismatch repair loss in cancer.DNA repair · 2025Review
- Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer.JCI insight · 2025Article
- Inhibition of histone methyltransferase EZH2 for immune interception of colorectal cancer in Lynch syndrome.JCI insight · 2025Article
- A novel mouse model recapitulating the MMR-defective SCLC subtype uncovers an actionable sensitivity to immune checkpoint blockade.Journal of cancer research and clinical oncology · 2024Article
- Prophylaxis with abemaciclib delays tumorigenesis in dMMR mice by altering immune responses and reducing immunosuppressive extracellular vesicle secretion.Translational oncology · 2024Article
- Colorectal cancer murine models: Initiation to metastasis.Cancer letters · 2024Review
- Loss of p53 and mutational heterogeneity drives immune resistance in an autochthonous mouse lung cancer model with high tumor mutational burden.Cancer cell · 2023Article
- Advancing translational research for colorectal immuno-oncology.British journal of cancer · 2023Review
- Mismatch repair deficiency is not sufficient to elicit tumor immunogenicity.Nature genetics · 2023Article
- The potential oncogenic effect of tissue-specific expression of JC polyoma T antigen in digestive epithelial cells.Transgenic research · 2023Article
- Mouse models in colon cancer, inferences, and implications.iScience · 2023Review
- Genetically engineered mouse models for hereditary cancer syndromes.Cancer science · 2023Review
- NADNature communications · 2023Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsMutations in the DNA mismatch repair (MMR) gene MSH2 cause Lynch syndromes I and II and sporadic colorectal cancers. Msh2(null) mice predominantly develop lymphoma and do not accurately recapitulate the colorectal cancer phenotype.
methodsWe generated and examined mice with a conditional Msh2 disruption (Msh2(LoxP)), permitting tissue-specific gene inactivation. ECMsh2(LoxP/LoxP) mice carried an EIIa-Cre transgene, and VCMsh2(LoxP/LoxP) mice carried a Villin-Cre transgene. We combined the VCMsh2(LoxP) allele with either Msh2(Delta7null) (VCMsh2(LoxP/null)) or Msh2(G674D) mutations (VCMsh2(LoxP/G674D)) to create allelic phase mutants. These mice were given cisplatin or 5-fluorouracil/leucovorin and oxaliplatin (FOLFOX), and their tumors were measured by magnetic resonance imaging.
resultsEmbryonic fibroblasts from ECMsh2(LoxP/LoxP) mice do not express MSH2 and are MMR deficient. Reverse transcription, polymerase chain reaction, and immunohistochemistry from VCMsh2(LoxP/LoxP) mice demonstrated specific loss of Msh2 messenger RNA and protein from epithelial cells of the intestinal tract. Microsatellite instability was observed in all VCMsh2 strains and limited to the intestinal mucosa. Resulting adenomas and adenocarcinomas had somatic truncation mutations to the adenomatous polyposis coli (Apc) gene. VCMsh2(LoxP/LoxP) mice did not develop lymphoma. Comparison of allelic phase tumors revealed significant differences in multiplicity and size. When treated with cisplatin or FOLFOX, tumor size was reduced in VCMsh2(LoxP/G674D) but not VCMsh2(LoxP/null) tumors. The apoptotic response to FOLFOX was partially sustained in the intestinal mucosa of VCMsh2(LoxP/G674D) animals.
conclusionsMsh2(LoxP/LoxP) mice in combination with appropriate Cre recombinase transgenes have excellent potential for preclinical modeling of Lynch syndrome, MMR-deficient tumors of other tissue types, and use in drug development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.