Conditional inactivation of the mouse Wwox tumor suppressor gene recapitulates the null phenotype |
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| Authors: | Suhaib K. Abdeen Sara Del Mare Sadeeq Hussain Muhannad Abu‐Remaileh Zaidoun Salah John Hagan Maysoon Rawahneh Xin‐an Pu Stacey Russell Janet L. Stein Gary S. Stein Jane B. Lian Rami I. Aqeilan |
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| Affiliation: | 1. Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University–Hadassah Medical School, Jerusalem, Israel;2. Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts;3. Al‐Quds‐Bard Honors College and Medical Research Center, Al‐Quds University, East Jerusalem‐Abu Dies, Palestine;4. Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, Ohio;5. Transgenic Core Facility, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio;6. Department of Biochemistry, University of Vermont, Burlington, Vermont |
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| 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. J. Cell. Physiol. 228: 1377–1382, 2013. © 2012 Wiley Periodicals, Inc. |
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