A mouse model of Wilms' Tumor

Background
The pediatric kidney cancer, Wilms tumor, is the fourth most common type of cancer in children. Wilms tumor seems to arise because of abnormalities in the formation of the kidneys from primitive cells in the embryo. The most studied genes mutated in Wilms tumor include WT1 and beta-catenin, which are essential for controlling the development of normal kidneys and in controlling how cells divide. However, these genes are only mutated in a small percentage of Wilms tumors.

In order to achieve a better understanding of this disease and ultimately to improve therapies, it is critical to identify and study additional genes that are mutated in this cancer. Recently, our collaborators discovered a new gene called WTX that is mutated with high frequency in Wilms tumor, and therefore is very important in causing this cancer. The function of this gene is currently unclear although some evidence suggests that there is a biological relationship between WTX and the beta-catenin and IGF2 genes. The elucidation of the function of this gene could give new insights into Wilms tumor therapies.

Project Goal
The goal of this proposal is to understand how mutations in WTX result in abnormalities in the kidneys leading to Wilms tumor. We used genetically engineering techniques to generate mice in which we can specifically create WTX mutations in the embryonic kidneys. We will study how WTX mutations affect normal kidney development in mice and in cells derived from mice. We will also determine how WTX mutations work with beta-catenin and IGF2 in controlling growth and cancer formation. Ultimately, these efforts will lead to a mouse model of Wilms tumor that will provide a valuable system in both understanding cancer biology and discovering and testing new therapies.