A mouse model for distal renal tubular acidosis reveals a previously unrecognized role of the V-ATPase a4 subunit in the proximal tubule

摘要: The V-ATPase is a multisubunit complex that transports protons across membranes. Mutations of its B1 or a4 subunit are associated with distal renal tubular acidosis and deafness. In the kidney, expressed in intercalated cells nephron, where controls acid/base secretion, proximal tubule cells, role less clear. Here, we report KO mice suffer not only from severe but also dysfunction defective endocytic trafficking, proteinuria, phosphaturia accumulation lysosomal material provide evidence these findings may be relevant patients. inner ear, co-localized pendrin at apical side epithelial lining endolymphatic sac. As were profoundly deaf displayed enlarged fluid compartments mirroring alterations mice, propose proton pump co-operate endolymph homeostasis. Thus, our mouse model gives new insights into divergent functions pathophysiology a4-related symptoms.