Myocardial YBX1 is dispensable for cardiac development and function.

The Y-box-binding protein 1 (YBX1) is a DNA- and RNA-binding protein with multifaceted roles in transcriptional, posttranscriptional, and translational regulation. Consequently, YBX1 controls many aspects of cellular function, including proliferation, differentiation, and apoptosis. In recent years, YBX1 emerged as an important player in the cardiovascular system, whose dysregulation underlies many forms of heart disease. Intriguingly, although reducing YBX1 levels in the myocardium confers protection against pathological cardiac remodeling, YBX1 knockdown in the heart also induces cardiac hypertrophy and fibrosis, raising safety concerns about targeting YBX1 therapeutically. Nevertheless, prior YBX1 loss-of-function studies used RNA interference (RNAi), which is susceptible to off-target effects and likely affected multiple cardiac cell types. Therefore, "clean" YBX1 cardiac-specific loss-of-function genetic models are required to delineate YBX1's precise role in the heart. To that end, we constructed both global and cardiomyocyte (CM)-specific