Alternately spliced WT1 antisense transcripts interact with WT1 sense RNA and show epigenetic and splicing defects in cancer.

Many mammalian genes contain overlapping antisense RNAs, but the functions and mechanisms of action of these transcripts are mostly unknown. WT1 is a well-characterized developmental gene that is mutated in Wilms' tumor (WT) and acute myeloid leukaemia (AML) and has an antisense transcript (WT1-AS), which we have previously found to regulate WT1 protein levels. In this study, we show that WT1-AS is present in multiple spliceoforms that are usually expressed in parallel with WT1 RNA in human and mouse tissues.

Wt1 is not essential for hematopoiesis in the mouse.

WT1 has been implicated in human leukemia and hematopoiesis, but its role in stem cell differentiation is not yet fully defined. We show that Wt1-null murine fetal liver cells are capable of reconstituting functional hematopoiesis following transplantation into irradiated recipients. There was also no significant difference between the in vitro colony-forming ability of wild-type and Wt1-null cells.

A WT1 exon 1 mutation in a child diagnosed with Denys-Drash syndrome.

Denys-Drash syndrome (DDS) is characterized by nephropathy, genital abnormalities, and predisposition to Wilms tumor. DDS is associated with constitutional WT1 mutations, the majority being missense mutations in the zinc-finger region. A dominant-negative mode of action of the mutant DDS proteins is thought to explain the more severe genitourinary phenotype seen in DDS compared with children with complete deletion of one WT1 allele.

Frequency and heritability of WT1 mutations in nonsyndromic Wilms' tumor patients: a UK Children's Cancer Study Group Study.

Purpose: Constitutional WT1 mutations in patients with Wilms' tumor (WT) have specifically been associated with genitourinary abnormalities, such as cryptorchidism and hypospadias. We sought to ascertain the frequency and heritability of constitutional WT1 mutations in nonsyndromic WT patients.

Patients And Methods: Constitutional DNA from 282 patients treated at seven United Kingdom Children's Cancer Study Group centers was screened for WT1 mutations using heteroduplex analysis.