Congenital anomalies of the kidney and urinary tract - Role of the loss offunction mutation in the pluripotent angiotensin type 2 receptor gene

Purpose: Recent studies of the human genome and genetic engineering experim ents in mice revealed that congenital anomalies of the kidney and urinary t ract commonly seen in newborns in various anatomical forms are polygenic di sease, that is a disease caused by simultaneous defects in multiple genes. We discuss some possible genetic explanations of the classic theories of th e formation of congenital kidney and urinary tract anomalies. Materials and Methods: We reviewed classic and current theories regarding u rinary tract development. Included in our review are recent results from ou r laboratory evaluating the genetic role of normal and abnormal urinary tra ct development. Results: We observed a genetic abnormality that may explain many classic an atomical theories of congenital kidney and urinary tract anomalies. One of the genes involved in urinary tract ontogenesis is the angiotensin type 2 r eceptor gene, which is the "other" angiotensin receptor. While the type 1 r eceptor mediates essentially all known actions of angiotensin, including it s hypertensive effect, relatively little is known about the angiotensin typ e 2 receptor. Careful dissection studies in mutant mouse embryos selectivel y lacking the angiotensin type 2 receptor gene revealed that this gene is p leiotropic, that is its defect causes not only ectopic ureteral budding fro m the wolffian duct, but also disturbance in other subsequent ontogenic eve nts that are critical for the normal growth of the kidney and urinary tract . Conclusions: Many congenital anomalies of the kidney and urinary tract appe ar to share a common genetic cause. While these anomalies are caused by var ious genetic hits, abnormalities in the angiotensin type 2 receptor gene ar e often involved in this anomalous development. This review article offers a better understanding of the genetics involved in urinary tract developmen t and ties some of the newly emerging genetic theories with classic anatomi cal theories.