Kids Kidney Research

Cystic kidney disease comprises a group of inherited conditions, also known as “ciliopathies” that lead to kidney failure and are a significant cause of childhood morbidity and mortality. Meckel‐Gruber syndrome (MKS) is the most severe ciliopathy involving cystic kidney disease that arises during embryonic development. MKS can be caused by changes in unique genes that code for two novel proteins called “MKS1” and "meckelin". Both proteins carry developmental signals from the outside to the inside of a kidney cell, controlling how the cell will behave during the formation of a nephron. This regulation is lost if these proteins are defective or absent. MKS is a ciliopathy because both the MKS1 and meckelin proteins are components of primary cilia. Cilia are finger‐like projections from cells that are thought to detect and respond to chemical or mechanical cues, such as fluid flow, during the formation of the nephron and other tubular structures. To further understand the molecular roles of MKS1 and meckelin in embryogenesis, we propose to study mice carrying the same defects as those that cause the human conditions. The work will provide key insights into how the normal developmental signals during nephron formation are lost in a severe cystic kidney disease. In these model systems, we will also be able to determine the effects of new drug treatments that are being proposed for cystic kidney diseases.