Conditional inactivation of the mouse Wwox tumor suppressor gene recapitulates the null phenotype

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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.

Original languageEnglish
Pages (from-to)1377-1382
Number of pages6
JournalJournal of Cellular Physiology
Volume228
Issue number7
DOIs
StatePublished - Jul 2013

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