CRISPR/Cas9-mediated nexilin deficiency interferes with cardiac contractile function in zebrafish in vivo.

ABSTRACT: Nexilin (NEXN) plays a crucial role in stabilizing the sarcomeric Z-disk of striated muscle fibers and, when mutated, leads to dilated cardiomyopathy in humans. Due to its early neonatal lethality in mice, the detailed impact of the constitutive homozygous NEXN knockout on heart and skeletal muscle morphology and function is insufficiently investigated. Here, we characterized a constitutive homozygous CRISPR/Cas9-mediated nexn knockout zebrafish model. We found that Nexn deficient embryos developed significantly reduced cardiac contractility and under stressed conditions also impaired skeletal muscle organization whereas skeletal muscle function seemed not to be affected. Remarkably, in contrast to nexn morphants, CRISPR/Cas9 nexn^-/- knockout embryos showed a milder phenotype wi

SUBMITTER: Hofeichner J 

PROVIDER: S-EPMC10730861 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature