Abstract Pathogenic variants in NONO are clinically linked to congenital heart disease (CHD), but in vivo mechanisms and gene-targeted interventions remain poorly explored. Using CRISPR/Cas9 gene editing and morpholino silencing, we established knockout (KO) and knockdown (KD) zebrafish models to study nono in cardiogenesis. Adult KO hearts displayed severe structural remodeling, characterized by ventricular distortion, disorganized sarcomeres, and myocardial fibrosis.
