Genetic deletion of Pax2 and Pax8 in adult mice

ABSTRACT: Background: The mammalian kidneys maintain salt and water homeostasis for proper electrolyte balance and hydration. As the glomerular filtrate passes through the nephron and into the renal medulla, electrolytes, water, and urea are reabsorbed through the concerted actions of solute carrier channels and aquaporins located at various positions along the nephron and in the outer and inner medulla. Renal epithelial cells develop from Pax2 positive proliferating stem cells that suppress Pax2 expression once differentiated into mature proximal and distal tubules, but continue to express the related Pax8 protein. The collecting tubules and renal medulla are derived from a Pax2 positive ureteric bud epithelia that continue to express Pax2 and Pax8 in adult kidneys. Despite the necessity for Pax2 in renal development, functions for Pax2 or Pax8 in adult renal epithelia have not been established. Methods: In this report, we deleted either Pax2, Pax8, or both genes in adult mice and examined the phenotypes and changes in gene expression patterns. The mechanism of Pax8 mediated activation of potential target genes was described in inner medullary collecting duct cells. Results: Mice with induced deletions of both Pax2 and Pax8 exhibit severe polyuria that can be attributed to significant changes in the expression of solute carriers, such as the urea transporter UTA1, and aquaporins within the inner and outer medulla. Furthermore, Pax8 expression is induced by high salt in collecting duct cells and activates the UTA1 gene by recruiting a histone methyltransferase complex to the promoter. Conclusions: These data uncover novel functions for Pax proteins, in adult renal epithelia, that are essential for retaining water and concentrating urine.

ORGANISM(S): Mus musculus

PROVIDER: GSE141455 | GEO | 2019/12/05

REPOSITORIES: GEO