A Micro-Engineered Heart Tissue Model of Desmin-related Cardiomyopathy Caused by Mutant αB Crystallin.

ABSTRACT: Protein quality control (PQC) is essential for maintaining sarcomere integrity in cardiomyocytes. α Crystallin B chain (CRYAB) R120G mutation disrupts CRYAB's chaperone activity, leading to aggregation of CRYAB and its client proteins (including Desmin), leading to Desmin-related cardiomyopathy (DRM). Prior experimental systems for modeling DRM linked to CRYAB require massive overexpression of CRYAB mutant isoforms, raising questions about translational relevance. Here, we establish the first model of CRYAB-linked DRM that uses genome-edited hiPSC together with isogenic controls, allowing us to study the impact of mutant CRYAB expressed at near endogenous levels. Within micro-engineered heart tissues (μHT), CRYAB-R120G mutant hiPSC-derived cardiomyocytes recapitulated key DRM hallmarks, in

SUBMITTER: Kargar Gaz Kooh Y 

PROVIDER: S-EPMC12621696 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature