Approximately 1% of newborns present with enlargement of the kidney that results from urine collection in the renal pelvis or calcyses. This can lead to obstructive nephropathy, the most common form of renal failure in infants and children. Obstructive nephropathy is often caused by structural blockage, due to the presence of stones. In many cases, however, the underlying cause seems to be a functional blockage, for which the molecular basis remains unknown. Feng Chen and colleagues, from Washington University School of Medicine, have developed a mouse model of this urinary tract disease by selectively deleting the Cnb1 gene from the mesenchyme of the developing urinary tract. Cnb1 is the regulatory subunit of calcineurin, a Ca2+-dependent serine/threonine phosphatase, which is thought to play a role in kidney function. The researchers found that selective deletion of Cnb1 resulted in a reduction in smooth muscle cell- and other mesenchymal cell-proliferation in the urinary tract, resulting in abnormal development of the renal pelvis and ureter. These defects inhibited normal pyeloureteral peristalsis -- a functional obstruction that ultimately leads to fatal renal failure. This study provides evidence for a direct role for the calcineurin-signaling pathway in urinary tract development and also shows the importance of functional rather than structural defects in the development of obstructive nephropathy.
A commentary by Cathy Medelsohn discusses the work by Chen and colleagues as it relates to our current understanding of kidney and urinary tract development and function.
TITLE: Calcineurin is required in urinary tract mesenchyme for the development of the pyeloureteral peristaltic machinery
Washington University School of Medicine, St. Louis, Missouri, USA.
Contact: Laurie Goodman
Journal of Clinical Investigation