Renal phenotype of Sortilin‐deficient mice (892.41)

Sortilin belongs to the family of the VPS10P‐domain receptors which mediate intracellular sorting of diverse ligands in various cell types. Sortilin is abundantly expressed in the kidney but little is known about its renal function. In this study we take advantage of sortilin‐deficient (Sort‐/‐) mice to test whether sortilin interferes with renal NaCl‐ or water reabsorption. To evaluate the role of sortilin in the kidney, sortilin‐deficient (Sort‐/‐) mice were analyzed for their physiologic kidney performance, kidney morphology, and biochemical profile of renal transporters. In wildtype (WT) mouse kidneys, sortilin has shown moderate expression in the distal nephron and strong expression in the principal cells of collecting duct. Sortilin deficiency had no major effects on kidney morphology. Physiologic evaluation of WT and Sort‐/‐ mice showed significantly increased urinary volume (+154%) upon sortilin disruption. Immunoblotting evaluation of distal epithelial salt transporters and water channels revealed that sortilin‐deficiency was associated with decreased levels of the Na‐Cl cotransporter (NCC) and of the phosphorylated, activated aquaporin 2. Our results suggest that sortilin facilitates the reabsorptive function of renal distal epithelia.