Cellular and electrophysiological characterization of triadin knockout syndrome using induced pluripotent stem cell-derived cardiomyocytes.

ABSTRACT: Triadin knockout syndrome (TKOS) is a malignant arrhythmia disorder caused by recessive null variants in TRDN-encoded cardiac triadin. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from two unrelated TKOS patients and an unrelated control. CRISPR-Cas9 gene editing was used to insert homozygous TRDN-p.D18fs^∗13 into a control line to generate a TKOS model (TRDN^-/-). Western blot confirmed total knockout of triadin in patient-specific and TRDN^-/- iPSC-CMs. iPSC-CMs from both patients revealed a prolonged action potential duration (APD) at 90% repolarization, and this was normalized by protein replacement of triadin. APD prolongation was confirmed in TRDN^-/- iPSC-CMs. TRDN^-/- iPSC-CMs revealed that loss of

SUBMITTER: Clemens DJ 

PROVIDER: S-EPMC10202692 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature