Genetic and developmental basis for urinary tract obstruction

Abstract

Urinary tract obstruction results in obstructive nephropathy and uropathy. It is the most frequent cause of renal failure in infants and children. In the past two decades, studies in transgenic models and humans have greatly enhanced our understanding of the genetic factors and developmental processes important in urinary tract obstruction. The emerging picture is that development of the urinary tract requires precise integration of a variety of progenitor cell populations of different embryonic origins. Such integration is controlled by an intricate signaling network that undergoes dynamic changes as the embryo develops. Most congenital forms of urinary tract obstruction result from the disruption of diverse factors and genetic pathways involved in these processes, especially in the morphogenesis of the urinary conduit or the functional aspects of the pyeloureteral peristaltic machinery.

The Leucine Zipper Putative Tumor Suppressor 2 Protein LZTS2 Regulates Kidney Development

“…mimic the human CAKUT that are the most common cause of renal failure in children (33,34). In addition, we also observed renal dysplasia, cystic disease, hydronephrosis, hydroureter, and collecting system duplication in Lzts2 null embryos, neonates, and adult mice.…”

Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney

“…We thus suspect that functional defects in handling urine transport or polyuria may be the primary cause of hydronephrosis, although other causes cannot be excluded at this point. [17][18][19] Absence of Adam10 in Collecting Duct Progenitor Cells Results in an Altered Ratio of PCs to ICs To distinguish the two main cell types in the collecting duct, namely the PCs and the ICs, we performed immunofluorescence staining on kidney sections with Aqp2 (a PC marker), and ATPase (an IC marker) (Figure 2, A-H). The proportion of ATPase + ICs was significantly higher in the mutants than in the controls (Figure 2, A-F and I).…”

“…Polyuria has the potential to eventually overwhelm the pyeloureteral peristaltic machinery for urine transfer, leading to hydronephrosis and renal failure. [17][18][19] Because the mice with hydronephrosis had various degrees of erosion of the renal parenchyma starting from the inner medulla, we analyzed these mice separately and focused mostly on the cortex, where structures were still relatively intact and recognizable. We found that the percentage of ATPase + ICs in the cortex was similar between mutants with hydronephrosis (46.51% 64.38%) and mutants without hydronephrosis (46.91% 65.49%) (P=0.68).…”

Plumbing the depths of urinary tract obstruction by using murine models

“…22 Continuing advances in mouse genetics and genomics will no doubt speed up the identification of the genetic factors and pathways involved in the pathogenesis of obstructive nephropathy.…”