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Updated: Oct 18, 2026

Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
Cellular Werner phenotypes in mice expressing a putative dominant-negative human WRN gene
1Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Abstract:
Mutations at the Werner helicase locus (WRN) are responsible for the Werner syndrome (WS). WS patients prematurely develop an aged appearance and various age-related disorders. We have generated transgenic mice expressing human WRN with a putative dominant-negative mutation (K577M-WRN). Primary tail fibroblast cultures from K577M-WRN mice showed three characteristics of WS cells: hypersensitivity to 4-nitroquinoline-1-oxide (4NQO), reduced replicative potential, and reduced expression of the endogenous WRN protein. These data suggest that K577M-WRN mice may provide a novel mouse model for the WS.
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