title: Cellular Werner phenotypes in mice expressing a putative dominant-negative human WRN gene.
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.
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: C E
authors.initials: CE
authors.lastname: Ogburn
authors.forename: C B
authors.initials: CB
authors.lastname: Ware
authors.forename: W C
authors.initials: WC
authors.lastname: Ladiges
authors.forename: H
authors.initials: H
authors.lastname: Youssoufian
authors.forename: G M
authors.initials: GM
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Oshima
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000031:analogs & derivatives / Q000494:pharmacology; D000483:Alleles; D000818:Animals; D002455:Cell Division; D004265:DNA Helicases / Q000235:genetics*; D015536:Down-Regulation; D005090:Exodeoxyribonucleases; D005799:Genes, Dominant; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D015363:Quinolones / Q000494:pharmacology; D053484:RecQ Helicases; D014898:Werner Syndrome / Q000235:genetics*; D000071657:Werner Syndrome Helicase
chemical_list: C120195:4-nitroquinolone-1-oxide; D015363:Quinolones; D015112:4-Nitroquinoline-1-oxide; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase