Plumbing the depths of urinary tract obstruction by using murine models

Abstract

Urinary tract obstruction leads to obstructive nephropathy, which in turn, frequently results in renal failure. Congenital urinary tract obstruction can be traced back to errors during the organogenesis of the urinary system. A fundamental understanding of the causes of urinary tract obstruction and the developmental processes involved are critical for improving the diagnostic and therapeutic strategies for this disease. A number of laboratories, including ours, have been using genetically engineered and spontaneously occurring mouse models to study the primary causes and the pathogenesis of urinary tract obstruction. These studies have shown that urinary tract obstruction is a very heterogeneous disease that can be caused by a diverse set of factors targeting multiple levels of the urinary system. Accumulating evidence also indicates that the development of the urinary tract requires the integration of progenitor cells of diverse embryonic origins, leading to the formation of multiple junctions prone to developmental errors. In addition, the high sensitivity of the pyeloureteral peristaltic machinery to disturbance affecting the structural or functional integrity of its components also contributes to the high incidence rate of urinary tract obstruction.