Role of KLF8 in Ventricular Chamber Development and Congenital Heart Defects

Congenital heart disease is the most common congenital defects, yet ~80% of cases lack a defined cause, underscoring the need for specific genetic determinants. KLFs have emerged as regulators of cardiovascular development and disease. In this project we show that KLF8 is expressed across the cardiac ventricular chambers during development and that KLF8 loss causes ventricular trabeculation and compaction defects with sex-biased timing: females around E14.5 seeming to improve by E17.5), males around E17.5, with partial perinatal male lethality. Suggesting compensatory mechanisms in females and some males. Thus, KLF8 emerges as a candidate regulator of chamber formation and CHD susceptibility.