Abstract
Using gene targeting in embryonic stem cells, we have derived mice with a null mutation in a DNA mismatch repair gene homolog, PMS2. We observed microsatellite instability in the male germline, in tail, and in tumor DNA of PMS2-deficient animals. We therefore conclude that PMS2 is involved in DNA mismatch repair in a variety of tissues. PMS2-deficient animals appear prone to sarcomas and lymphomas. PMS2-deficient males are infertile, producing only abnormal spermatozoa. Analysis of axial element and synaptonemal complex formation during prophase of meiosis I indicates abnormalities in chromosome synapsis. These observations suggest links among mismatch repair, genetic recombination, and chromosome synapsis in meiosis.
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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Adenosine Triphosphatases*
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Alleles
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Amino Acid Sequence
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Animals
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Base Composition
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Base Sequence
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Chromosome Aberrations*
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Chromosome Disorders*
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Cloning, Molecular
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DNA / genetics
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DNA Primers
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DNA Repair / genetics*
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DNA Repair Enzymes*
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DNA-Binding Proteins*
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Embryo, Mammalian / physiology
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Female
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Genetic Predisposition to Disease
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Genotype
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Humans
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Lymphoma / genetics
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Male
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Meiosis / genetics
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Mice
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Mice, Mutant Strains
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Mismatch Repair Endonuclease PMS2
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Molecular Sequence Data
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Oligodeoxyribonucleotides
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Polymerase Chain Reaction
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Protein Biosynthesis
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Proteins / chemistry
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Proteins / genetics*
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Recombinant Proteins / biosynthesis
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Restriction Mapping
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Sarcoma / genetics
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Seminiferous Tubules / pathology
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Sequence Homology, Amino Acid
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Spermatocytes / pathology
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Spermatocytes / ultrastructure
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Spermatozoa / pathology
Substances
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DNA Primers
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DNA-Binding Proteins
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Oligodeoxyribonucleotides
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Proteins
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Recombinant Proteins
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DNA
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Adenosine Triphosphatases
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PMS2 protein, human
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Pms2 protein, mouse
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Mismatch Repair Endonuclease PMS2
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DNA Repair Enzymes