RNA-seq analysis of cardiomyocyte-specific Flnc deficiency and AAV-mediated FLNC reconstitution in mouse hearts

These variants are associated with progressive ventricular dysfunction, malignant ventricular arrhythmias, heart failure, and an increased risk of sudden cardiac death. Although current clinical therapies can alleviate symptoms and reduce arrhythmic burden, they do not directly restore FLNC expression or address the underlying molecular defect.

To investigate the transcriptional consequences of FLNC deficiency and the molecular effects of FLNC restoration, we performed bulk RNA sequencing on ventricular tissues from control mice, cardiomyocyte-specific inducible Flnc knockout (iCKO) mice, and iCKO mice treated with a 3-intein adeno-associated virus (AAV) system designed to reconstitute full-length FLNC expression. Comparative transcriptomic analyses identified gene expression changes associated with Flnc deficiency and their modulation following AAV-mediated FLNC replacement.