Abstract
Alterations of the human MSH2 gene, a homologue of the bacterial MutS mismatch repair gene, co-segregate with the majority of hereditary non-polyposis colon cancer (HNPCC) cases. We have generated homozygous MSH2-/- mice. Surprisingly, these mice were found to be viable, produced offspring in a mendelian ratio and bred through at least two generations. Starting at two months of age homozygous-/- mice began, with high frequency, to develop lymphoid tumours that contained microsatellite instabilities. These data establish a direct link between MSH2 deficiency and the pathogenesis of cancer. These mutant mice should be good models to study the progression of tumours and also to screen carcinogenic and anti-cancer agents.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Cell Transformation, Neoplastic / genetics
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Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
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DNA Repair / genetics*
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DNA, Neoplasm / analysis*
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DNA, Neoplasm / genetics
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DNA, Satellite / analysis*
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DNA-Binding Proteins / genetics*
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Female
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Fungal Proteins*
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Gene Targeting*
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Genotype
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Humans
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Lymphoid Tissue / pathology
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Male
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Meiosis
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Mice
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Mice, Knockout
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Mice, Mutant Strains
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Molecular Sequence Data
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MutS Homolog 2 Protein
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Species Specificity
Substances
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DNA, Neoplasm
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DNA, Satellite
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DNA-Binding Proteins
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Fungal Proteins
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MutS Homolog 2 Protein