- Center for Metabolism and Immunity
Interdisciplinary Research Initiative
2/1/2011 - 1/31/2014
Congenital abnormalities of the kidney and urinary tract occur in one out of 500 newborns and are the most frequent cause of chronic kidney disease in children. However, very little is known about the underlying causes of this group of birth defects. In mice, recent studies have shown that absence of the DLG1 gene, which encodes a protein that regulates cell structure and cell-cell interactions during development, leads to urologic abnormalities and occasionally malformed kidneys. Dr. Ahn, a pediatric nephrologist, discovered that the absence of both DLG1 and a second protein, CASK, that interacts with DLG1, results in much more severe kidney malformations. This proposal will follow up on this exciting observation. One aim is to determine the specific molecular functions of DLG1 and CASK and how they interact to regulate kidney development, using mice with defects in these genes engineered to affect their expression in specific cell types. The second aim is to search for mutations in DLG1, CASK, and related pathways in children with kidney and urinary tract anomalies. Overall, these studies will lead to a better understanding of how congenital kidney and urologic defects arise, whether similar genes are affected in humans, and could provide clinicians and patients with tools for early diagnosis and genetic counseling, and in the future, possible therapeutic strategies. The project includes a collaboration with Jeffrey Miner, PhD in the Department of Medicine, who is an expert in kidney function and development and will help with generating mutant mice and their analysis.