A potent antagonist antibody targeting connexin hemichannels alleviates Clouston syndrome symptoms in mutant mice.

ABSTRACT:

Background

Numerous currently incurable human diseases have been causally linked to mutations in connexin (Cx) genes. In several instances, pathological mutations generate abnormally active Cx hemichannels, referred to also as "leaky" hemichannels. The goal of this study was to assay the in vivo efficacy of a potent antagonist antibody targeting Cx hemichannels.

Methods

We employed the antibody to treat Cx30^A88V/A88V adult mutant mice, the only available animal model of Clouston syndrome, a rare orphan disease caused by Cx30 p.A88V leaky hemichannels. To gain mechanistic insight into antibody action, we also performed patch clamp recordings, Ca²⁺ imaging and ATP release assay in vitro.

Findings

Two weeks of antibody treatment sufficed to repress

SUBMITTER: Kuang Y 

PROVIDER: S-EPMC7378960 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature