Mutations in the WRN gene in mice accelerate mortality in a p53-null background.
Document Type
Article
Publication Date
2000
Keywords
Blotting-Western, Camptothecin, Cell-Aging, Cell-Division, Cells-Cultured, Cloning-Molecular, Dose-Response-Relationship-Drug, DNA-Helicases, Embryo, Fibroblasts, Gene-Library, Life-Expectancy, Mice, Mice-Knockout, Molecular-Sequence-Data, Mutation, Phenotype, Protein-p53, Quinolones, Spleen, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Time-Factors, Tissue-Distribution, 4-Nitroquinoline-1-oxide
First Page
3286
Last Page
3291
JAX Source
Mol Cell Biol 2000 May; 20(9):3286-91.
Abstract
Werner's syndrome (WS) is a human disease with manifestations resembling premature aging. The gene defective in WS, WRN, encodes a DNA helicase. Here, we describe the generation of mice bearing a mutation that eliminates expression of the C terminus of the helicase domain of the WRN protein. Mutant mice are born at the expected Mendelian frequency and do not show any overt histological signs of accelerated senescence. These mice are capable of living beyond 2 years of age. Cells from these animals do not show elevated susceptibility to the genotoxins camptothecin or 4-NQO. However, mutant fibroblasts senesce approximately one passage earlier than controls. Importantly, WRN(-/-);p53(-/-) mice show an increased mortality rate relative to WRN(+/-);p53(-/-) animals. We consider possible models for the synergy between p53 and WRN mutations for the determination of life span.
Recommended Citation
Lombard DB,
Beard C,
Johnson B,
Marciniak RA,
Dausman J,
Bronson R,
Buhlmann JE,
Lipman R,
Curry R,
Sharpe A,
Jaenisch R,
Guarente L.
Mutations in the WRN gene in mice accelerate mortality in a p53-null background. Mol Cell Biol 2000 May; 20(9):3286-91.