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

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 postnata...

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Bibliographic Details
Published in:Journal of cellular physiology 2013-07, Vol.228 (7), p.1377-1382
Main Authors: Abdeen, Suhaib K., Del Mare, Sara, Hussain, Sadeeq, Abu-Remaileh, Muhannad, Salah, Zaidoun, Hagan, John, Rawahneh, Maysoon, Pu, Xin-an, Russell, Stacey, Stein, Janet L., Stein, Gary S., Lian, Jane B., Aqeilan, Rami I.
Format: Article
Language:English
Subjects:
Age
Animal models
Animals
Calcification, Physiologic - genetics
Calcification, Physiologic - physiology
Developmental stages
Female
Gene Expression Regulation, Developmental
Gene Targeting
Genes, Tumor Suppressor
Humans
Inactivation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mineralization
Models, Animal
Osteosarcoma - genetics
Osteosarcoma - pathology
Oxidoreductases - antagonists & inhibitors
Oxidoreductases - genetics
Oxidoreductases - physiology
Phenotype
Steroids - biosynthesis
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - physiology
WW Domain-Containing Oxidoreductase
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Summary: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.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.24308