ROBO4 and aortic aneurysm: This included in vitro studies that showed that ROBO4 variant alleles disrupt endothelial barrier function, a mouse knockout for Robo4 that developed BAV and aortic aneurysm, and most impressively, a mouse knock-in of the specific variant that was identified in the original family, which also developed BAV and aortic aneurysm [166].