Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all αv integrins

alpha v integrins have been implicated in many developmental processes and are therapeutic targets for inhibition of angiogenesis and osteoporosis. Surprisingly, ablation of the gene for the alpha v integrin subunit, eliminating all five alpha v integrins, although causing lethality, allows considerable development and organogenesis including, most notably, extensive vasculogenesis and angiogenesis. Eighty percent of embryos die in midgestation, probably because of placental defects, but all embryos develop normally to E9.5, and 20% are born alive. These liveborn alpha v-null mice consistently exhibit intracerebral and intestinal hemorrhages and cleft palates. These results necessitate reevaluation of the primacy of alpha v integrins in many functions including vascular development, despite reports that blockade of these integrins with antibodies or peptides prevents angiogenesis.