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      Defective angiogenesis in mice lacking endoglin.

      Science (New York, N.Y.)
      Animals, Antigens, CD, Antigens, CD31, analysis, Blood Vessels, cytology, embryology, metabolism, Cell Differentiation, Crosses, Genetic, Endothelium, Vascular, Female, Gene Targeting, In Situ Hybridization, Male, Mice, Mice, Inbred C57BL, Microscopy, Electron, Muscle, Smooth, Vascular, Neovascularization, Physiologic, Receptors, Cell Surface, Signal Transduction, Transforming Growth Factor beta, Vascular Cell Adhesion Molecule-1, genetics, physiology, Yolk Sac, ultrastructure

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          Abstract

          Endoglin is a transforming growth factor-beta (TGF-beta) binding protein expressed on the surface of endothelial cells. Loss-of-function mutations in the human endoglin gene ENG cause hereditary hemorrhagic telangiectasia (HHT1), a disease characterized by vascular malformations. Here it is shown that by gestational day 11.5, mice lacking endoglin die from defective vascular development. However, in contrast to mice lacking TGF-beta, vasculogenesis was unaffected. Loss of endoglin caused poor vascular smooth muscle development and arrested endothelial remodeling. These results demonstrate that endoglin is essential for angiogenesis and suggest a pathogenic mechanism for HHT1.

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