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Targeting the WRN Locus in the mouse

  • David B. Lombard

Abstract

Werner syndrome (WS) is an autosomal recessive disorder typified by many symptoms of premature aging. The gene defective in WS, WRN, has been cloned and encodes a novel member of the RecQ DNA helicase family. Here the cloning of a highly conserved murine homolog of WRN, mWRN, is described. Unlike the human WRN protein, which is concentrated in the nucleolus, mWRN is distributed throughout the nucleus. Mice lacking the mWRN protein are viable and fertile and fail to demonstrate any signs of premature aging. Mutant fibroblasts senesce earlier than wild type. mWRN−/−; p53−/− animals show increased mortality relative to mWRN+/−; p53−/− mice. Possible reasons for the discrepancies between the WRN knockout mouse described here and that generated by others are discussed, as well as explanations for the differences in phenotypic consequences between WS in humans and targeted mutations in mWRN in the mouse.

Some of the mouse data in this chapter has been previously published: Lombard DB, Beard C, Johnson B et al (2000): Mutations in the WRN gene in mice accelerate mortality in a p53-null background. MCB 20:3286–3291. Used by permission.

The immunofluorescence presented in this chapter has been previously published: Marciniak RA, Lombard, DB, Johnson, FB, and L Guarente (1998): Nucleolar localization of the Werner syndrome protein in human cells. PNAS 95:6887–6892. Used by permission.

Keywords

Premature Aging Mutant Animal Werner Syndrome Helicase Domain Werner Syndrome Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • David B. Lombard
    • 1
  1. 1.Massachusetts Institute of TechnologyUSA

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