Integrated multi-omics approach revealed TTNtv c.13254T>G causing dilated cardiomyopathy in mice.

ABSTRACT: Titin-truncating variant (TTNtv) is the most common genetic cause of dilated cardiomyopathy (DCM). In the previous study, we found a novel heterozygous TTNtv c.13254T>G (p.Tyr4418Ter) associated with DCM, but lacking functional evidence. The purpose of this study is to demonstrate the pathogenicity of TTNtv c.13254T>G. We constructed a mouse model with TTNtv Y4370* on exon 45 by CRISPR/Cas9-mediated genome engineering to imitate the TTNtv. c.13254T>G. Transmission electron microscope (TEM), immunohistochemistry, western blot (WB), Transcriptome sequencing (RNA-seq), and tandem Mass Tag (TMT) proteome analysis were performed on the mutant (KO) and WT mice cardiac tissue. Multi-omics association analysis was performed to observe the damages of cardiac tissue, and changes of inflammatory fact

SUBMITTER: Yu D 

PROVIDER: S-EPMC11452030 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature