Intercalated Cell Depletion and Vacuolar H⁺-ATPase Mistargeting in an Ae1 R607H Knockin Model.

ABSTRACT: Distal nephron acid secretion is mediated by highly specialized type A intercalated cells (A-ICs), which contain vacuolar H⁺-ATPase (V-type ATPase)-rich vesicles that fuse with the apical plasma membrane on demand. Intracellular bicarbonate generated by luminal H⁺ secretion is removed by the basolateral anion-exchanger AE1. Chronically reduced renal acid excretion in distal renal tubular acidosis (dRTA) may lead to nephrocalcinosis and renal failure. Studies in MDCK monolayers led to the proposal of a dominant-negative trafficking mechanism to explain AE1-associated dominant dRTA. To test this hypothesis in vivo, we generated an Ae1 R607H knockin mouse, which corresponds to the most common dominant dRTA mutation in human AE1, R589H. Compared with wild-type mice

SUBMITTER: Mumtaz R 

PROVIDER: S-EPMC5407715 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature