4-Phenylbutyric Acid Treatment Reduces Low-Molecular-Weight Proteinuria in a Clcn5 Knock-in Mouse Model for Dent Disease-1.

ABSTRACT: Dent disease-1 (DD-1) is a rare X-linked tubular disorder characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and nephrocalcinosis. This disease is caused by inactivating mutations in the CLCN5 gene which encodes the voltage-gated ClC-5 chloride/proton antiporter. Currently, the treatment of DD-1 is only supportive and focused on delaying the progression of the disease. Here, we generated and characterized a Clcn5 knock-in mouse model that carries a pathogenic CLCN5 variant, c. 1566_1568delTGT; p.Val523del, which has been previously detected in several DD-1 unrelated patients, and presents the main clinical manifestations of DD-1 such as high levels of urinary b2-microglobulin, phosphate and calcium. Mutation p.Val523del causes par

SUBMITTER: Perdomo-Ramirez A 

PROVIDER: S-EPMC11311629 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature