Generation of a homozygous CRYAB p.Arg120Gly mutant (UKEi001-A-1) from a human iPSC line

Abstract

Variants in CRYAB can lead to desmin-related (cardio-)myopathy (DRM), a genetic muscle disorder with no curative treatment available. We introduced a homozygous CRYAB c.358G > A (p.Arg120Gly) mutation, which is established for the study of DRM in mice, into a donor human induced pluripotent stem cell (hiPSC) line. Control and mutant hiPSCs were tested for karyotype integrity and pluripotency marker expression. HiPSCs could be differentiated into endoderm, ectoderm and cardiomyocytes as a mesodermal derivative in vitro. CRYABhom hiPSC-derived cardiomyocytes developed intracellular CRYAB aggregates, which is a hallmark of DRM. This newly created mutant can be utilized to study DRM and cardiac proteinopathy in a human context.