Characterization of the Wilms tumor suppressor gene X (WTX) in tumorigenesis and normal kidney development of the mouse

• Applicant: Dr. Alexa Burger
• Subject Area: Nephrology
• Term: from 2008 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 84743245

Wilms tumor is the most common pediatric kidney cancer and closely associated with renal organogenesis. Various genes associated with kidney development are found inappropriately inactivated in Wilms tumor, e.g. WT1, while others appear activated, such as CTNNB1, encoding a component of the Wnt signaling pathway; however, for the majority of Wilms tumor, no consistently specific aberrations have been detected. Recently, this obstacle could be overcome through the discovery of a novel inactivated gene in 30% of Wilms tumor, which is located on the X chromosome and named WTX. The aim of this project is to study inactivated WTX in the mouse to identify and characterize its influence during nephrogenesis. For this purpose, I will use a conditional WTX knockout mouse, which allows temporal and tissue-specific expression of WTX, and also will allow me to establish an in vivo Wilms tumor model based on WTX loss-of-function. I will use this genetic tool to show the significant relevance of WTX in this pediatric cancer as well as in normal nephrogenesis. In summary, the analysis of WTX will allow conclusions about its biological function, involved molecular mechanisms and pathways, as well as its contribution to tumorigenic events in renal precursor cells.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Daniel A. Haber