Effects of constitutively active IKKβ on cardiac development

Abstract

NF-κB is a major transcription factor regulating cell survival, organ development and inflammation, but its role in cardiac development has been inadequately explored. To examine this function, we generated mice in which IKKβ, an essential kinase for NF-κB activation, was constitutively activated in embryonic cardiomyocytes. For this purpose, we used smooth muscle-22α (SM22α)-Cre mice, which are frequently used for gene recombination in embryonic cardiomyocytes. Embryonic hearts of SM22αCre-CA (constitutively active) IKKβflox/flox mice revealed remarkably thin, spongy and hypoplastic myocardium. In exploring the mechanism, we found that the expression of bone morphogenetic protein 10 (BMP10) and T-box transcription factor 20 (Tbx20), major regulators of cardiac development, was significantly downregulated and upregulated, respectively, in the SM22αCre-CAIKKβflox/flox mice. We also generated NK2 homeobox 5 (Nkx2.5) Cre-CAIKKβflox/wt mice since Nkx2.5 is also expressed in embryonic cardiomyocytes and confirmed that the changes in these genes were also observed. These results implicated that the activation of NF-κB affects cardiac development.