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The tumor suppressor gene we are particularly interested in is the Wilms tumor suppressor gene WT1. Expression of WT1 is required for normal development of the gonads, the kidney and mesothelial structures. Inactivation of WT1 is an early event in tumorigenesis. The WT1 gene encodes a transcription factor of the zinc finger family. For a long time WT1 has been considered as a transcriptional repressor. However, more recently WT1 has been shown to activate a number of target genes. Using conditional alleles of WT1 in cell-based assays as well as by comparison of wildtype and WT1-/- animals we are trying to identify additional target genes for the various splice forms of WT1. In an additional biochemical approach we are also trying to define and characterize interacting proteins of WT1. |
| A second major aspect of our WT1-work comprises the characterization of its role in vivo. For that we have crossed the WT1-knockout mouse into additional genetic backgrounds. We have used these strains to show that in addition to its requirement for the formation of the kidney and the gonads, WT1 is needed for the development of the spleen, thereby extending the role of this gene in organ development. We are currently using these mice, which - compared to the original knockout mouse - show an extended lifespan, to elucidate the role of WT1 in the genesis of different organs with particular emphasis on early sex development. |
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