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Conditional inactivation of the mouse Wwox tumor suppressor gene recapitulates the null phenotype
Author(s) -
Abdeen Suhaib K.,
Del Mare Sara,
Hussain Sadeeq,
AbuRemaileh Muhannad,
Salah Zaidoun,
Hagan John,
Rawahneh Maysoon,
Pu Xinan,
Russell Stacey,
Stein Janet L.,
Stein Gary S.,
Lian Jane B.,
Aqeilan Rami I.
Publication year - 2013
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24308
Subject(s) - wwox , chromosomal fragile site , suppressor , biology , cancer research , phenotype , conditional gene knockout , gene , tumor suppressor gene , exon , germline , microbiology and biotechnology , genetics , carcinogenesis , chromosome
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.