Title

Targeted ablation of the WW domain-containing oxidoreductase tumor suppressor leads to impaired steroidogenesis

UMMS Affiliation

Department of Cell Biology

Publication Date

2009-03-01

Document Type

Article

Subjects

Animals; Female; Follicle Stimulating Hormone; Gene Deletion; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Genes, Tumor Suppressor; Luteinizing Hormone; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutagenesis, Site-Directed; Oligonucleotide Array Sequence Analysis; Ovary; Oxidoreductases; Pituitary Gland; Steroids; Testis

Disciplines

Cell Biology

Abstract

The WW domain-containing oxidoreductase (WWOX) gene encodes a 46-kDa tumor suppressor. The Wwox protein contains two N-terminal WW domains that interact with several transcriptional activators containing proline-tyrosine motifs and a central short-chain dehydrogenase/reductase domain that has been suggested to play a role in steroid metabolism. Recently, we have shown that targeted deletion of the Wwox gene in mice leads to postnatal lethality and defects in bone growth. Here, we report that Wwox-deficient mice display impaired steroidogenesis. Mutant homozygous mice are born with gonadal abnormalities, including failure of Leydig cell development in testis and reduced theca cell proliferation in ovary. Furthermore, Wwox(-/-) mice displayed impaired gene expression of key steroidogenesis enzymes. Affymetrix microarray gene analysis revealed differentially expressed related genes in steroidogenesis in knockout mice testis and ovary as compared with control mice. These results demonstrate the essential requirement for the Wwox tumor suppressor in proper steroidogenesis.

DOI of Published Version

10.1210/en.2008-1087

Source

Endocrinology. 2009 Mar;150(3):1530-5. Epub 2008 Oct 30. Link to article on publisher's site

Journal/Book/Conference Title

Endocrinology

Related Resources

Link to Article in PubMed

PubMed ID

18974271

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