Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins.
alphav 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 alphav integrin subunit, eliminating all five alphav integrins, although causing lethality, allows considerable development and organogenesis including, most notably, extensive vasculogenesis and angiogenesis. Eighty percent of embryos die in mid-gestation, probably because of placental defects, but all embryos develop normally to E9.5, and 20% are born alive. These liveborn alphav-null mice consistently exhibit intracerebral and intestinal hemorrhages and cleft palates. These results necessitate reevaluation of the primacy of alphav integrins in many functions including vascular development, despite reports that blockade of these integrins with antibodies or peptides prevents angiogenesis.
Bader
B L
BL
Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, Massachusetts 02139, USA.
Rayburn
H
H
Crowley
D
D
Hynes
R O
RO
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002543:Cerebral Hemorrhage / Q000196:embryology; D002678:Chimera; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005804:Genes, Lethal; D006720:Homozygote; D039564:Integrin alphaV; D016023:Integrins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D039564:Integrin alphaV; D016023:Integrins