title: Conditional inactivation of the mouse Wwox tumor suppressor gene recapitulates the null phenotype.
abstract: WW domain-containing oxidoreductase (WWOX) is highly conserved in both human and murine. WWOX spans the second most common human chromosomal fragile site, FRA16D, and is commonly inactivated in multiple human cancers. Modeling WWOX inactivation in mice revealed a complex phenotype including postnatal lethality, defects in bone metabolism and steroidogenesis and tumor suppressor function resulting in osteosarcomas. For better understanding of WWOX roles in different tissues at distinct stages of development and in pathological conditions, Wwox conditional knockout mice were generated in which loxp sites flank exon 1 in the Wwox allele. We demonstrated that Cre-mediated recombination using EIIA-Cre, a Cre line expressed in germline, results in postnatal lethality by age of 3 weeks and decreased bone mineralization resembling total ablation of WWOX as in conventional null mice. This animal model will be useful to study distinct roles of WWOX in multiple tissues at different ages.
authors.affiliation: Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Suhaib K
authors.initials: SK
authors.lastname: Abdeen
authors.forename: Sara
authors.initials: S
authors.lastname: Del Mare
authors.forename: Sadeeq
authors.initials: S
authors.lastname: Hussain
authors.forename: Muhannad
authors.initials: M
authors.lastname: Abu-Remaileh
authors.forename: Zaidoun
authors.initials: Z
authors.lastname: Salah
authors.forename: John
authors.initials: J
authors.lastname: Hagan
authors.forename: Maysoon
authors.initials: M
authors.lastname: Rawahneh
authors.forename: Xin-An
authors.initials: XA
authors.lastname: Pu
authors.forename: Stacey
authors.initials: S
authors.lastname: Russell
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.forename: Rami I
authors.initials: RI
authors.lastname: Aqeilan
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000235:genetics / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D013256:Steroids / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D013256:Steroids; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; C428130:Wwox protein, mouse