Functional rescue of periodic paralysis by in vivo gene editing of CaV1.1

Abstract

Missense mutations of CaV1.1 cause hypokalemic periodic paralysis (HypoPP) by creating an anomalous leak—the gating pore current—that renders the fiber susceptible to paradoxical depolarization and loss of excitability in low extracellular K+. We previously generated CaV1.1-R528H knock-in mutant mice and validated a robust HypoPP phenotype when challenged by 2 mM K+. In this study, we tested the feasibility of gene editing technologies to rescue the HypoPP phenotype in our R528H mouse model.