Nephropathy and defective spermatogenesis in mice transgenic for a single isoform of the Wilms' tumour suppressor protein, WT1−KTS, together with one disrupted Wt1 Allele

Diya Lahiri, James R Dutton, Antonio Duarte, Kim Moorwood, Christopher F Graham, Andrew Ward

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The Wilms' tumour suppressor protein, WT1, is a zinc finger protein essential for the development of several organs, including the kidney and gonads. In each of these tissues WT1 is required at multiple stages of development and its persistent expression in podocytes and Sertoli cells suggests WT1 may also have a role in the maintenance of kidney and testis function throughout adult life. Naturally occurring isoforms of WT1 are generated by alternative mRNA splicing. An altered ratio of the splice isoforms WT1−KTS and WT1 + KTS appears to be sufficient to account for the developmental abnormalities (pseudohermaphroditism and nephropathy) characteristic of Frasier syndrome. We show that mice with a transgene encoding WT1−KTS do not differ from their wild-type littermates unless they are also heterozygous for a null mutation at the endogenous Wt1 locus. Animals with both genetic modifications develop proteinuria, together with multiple glomerular cysts, and male infertility. These pathologic changes may be explained as a consequence of altering the WT1 isoform ratio in tissues that express WT1 during adulthood. The results suggest WT1 misexpression could contribute to human glomerulocystic kidney disease
Original languageEnglish
Pages (from-to)300-311
Number of pages12
JournalMolecular Reproduction and Development
Volume74
Issue number3
DOIs
Publication statusPublished - 2006

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Tumor Suppressor Proteins
Wilms Tumor
Spermatogenesis
Transgenic Mice
Protein Isoforms
Alleles
Frasier Syndrome
Kidney
Disorders of Sex Development
Podocytes
Sertoli Cells
Male Infertility
Zinc Fingers
Alternative Splicing
Kidney Diseases
Gonads
Transgenes
Proteinuria
Testis
Cysts

Cite this

Nephropathy and defective spermatogenesis in mice transgenic for a single isoform of the Wilms' tumour suppressor protein, WT1−KTS, together with one disrupted Wt1 Allele. / Lahiri, Diya; Dutton, James R; Duarte, Antonio; Moorwood, Kim; Graham, Christopher F; Ward, Andrew.

In: Molecular Reproduction and Development, Vol. 74, No. 3, 2006, p. 300-311.

Research output: Contribution to journalArticle

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