EXTENSIVE VASCULOGENESIS, ANGIOGENESIS, AND ORGANOGENESIS PRECEDE LETHALITY IN MICE LACKING ALL ALPHA-V INTEGRINS

alpha v integrins have been implicated in many developmental processes and are therapeutic targets for inhibition of angiogenesis and osteop orosis. Surprisingly, ablation of the gene for the alpha v integrin su bunit, eliminating all five alpha v integrins, although causing lethal ity, allows considerable development and organogenesis including, most notably, extensive vasculogenesis and angiogenesis. Eighty percent of embryos die in midgestation, probably because of placental defects, b ut all embryos develop normally to E9.5, and 20% are born alive. These liveborn alpha v-null mice consistently exhibit intracerebral and int estinal hemorrhages and cleft palates. These results necessitate reeva luation of the primacy of alpha v integrins in many functions includin g vascular development, despite reports that blockade of these integri ns with antibodies or peptides prevents angiogenesis.