Transcriptome changes of whole kidney from conditional Vhl gene knockout in sub-populations of mouse kidney tubule cells

We are studying a tumor suppressor gene, von Hippel-Lindau (VHL). In humans, VHL mutations cause renal cell carcinoma of the clear cell type (ccRCC). We have generated a knockout mouse strain in which mouse Vhl is conditionally deleted in the kidney epithelium (that is, a subset of tubules including collecting ducts and ascending loop of Henle). Instead of ccRCC, these mice developed severe inflammation and fibrosis, accompanied by hyperplasia and the appearance of transformed clear cells. These phenotypes therefore support the notion that inflammation is the tissue precondition of cancer. Our hypothesis is that VHL loss-of-function-induced inflammation contribute to the initiation of carcinogenesis, through a mechanism that we want to determine. The aim of the microarray is to identify genes involved in the overgrowth of the epithelium, as well as in inflammation and fibrosis that may be important for ccRCC initiation.

6