Cellular Werner phenotypes in mice expressing a putative dominant-negativehuman WRN gene

Mutations at the Werner helicase locus (WRN) are responsible for the Werner syndrome (WS). WS patients prematurely del clop an aged appearance and var ious age-related disorders. We have generated transgenic mice expressing hu man WRN with a putative dominant-negative mutation (K577M-WRN). Primary tai l fibroblast cultures fi-om K577M-WRN mice showed three characteristics of WS cells: hypersensitivity to 4-nitroquinoline-1-oxide (4NQO), reduced repl icative potential, and reduced expression of the endogenous WRN protein. Th ese data suggest that K577M-WRN mice may provide a novel mouse model for th e WS.