Cellular Werner Phenotypes in Mice Expressing a Putative Dominant-Negative Human WRN Gene

Cellular Werner Phenotypes in Mice Expressing a Putative Dominant-Negative Human WRN Gene

Lan Wang^a,b, Charles E. Ogburn^b, Carol B. Ware^c, Warren C. Ladiges^c, Hagop Youssoufian^d, George M. Martin^a,b, and Junko Oshima^a
^a Department of Pathology, University of Washington, Seattle, Washington 98195
^b Department of Genetics, University of Washington, Seattle, Washington 98195
^c Department of Comparative Medicine, University of Washington, Seattle, Washington 98195
^d Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030

Corresponding author: Junko Oshima, Box 357470, Health Science Bldg. K543, Department of Pathology, University of Washington, 1959 NE Pacific Ave., Seattle, WA 98195-7470., picard{at}u.washington.edu (E-mail)

Communicating editor: R. S. HAWLEY

Mutations at the Werner helicase locus (WRN) are responsiblefor the Werner syndrome (WS). WS patients prematurely developan aged appearance and various age-related disorders. We havegenerated transgenic mice expressing human WRN with a putativedominant-negative mutation (K577M-WRN). Primary tail fibroblastcultures from K577M-WRN mice showed three characteristics ofWS cells: hypersensitivity to 4-nitroquinoline-1-oxide (4NQO),reduced replicative potential, and reduced expression of theendogenous WRN protein. These data suggest that K577M-WRN micemay provide a novel mouse model for the WS.

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