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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD
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Blood Vessels / cytology
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Blood Vessels / embryology*
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Blood Vessels / metabolism
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Cell Differentiation
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Crosses, Genetic
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Endoglin
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Endothelium, Vascular / cytology
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Endothelium, Vascular / embryology*
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Endothelium, Vascular / metabolism
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Female
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Gene Targeting
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In Situ Hybridization
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Male
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Mice
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Mice, Inbred C57BL
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Microscopy, Electron
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / embryology*
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Neovascularization, Physiologic*
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Platelet Endothelial Cell Adhesion Molecule-1 / analysis
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Receptors, Cell Surface
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Signal Transduction
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Transforming Growth Factor beta / metabolism
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / physiology*
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Yolk Sac / ultrastructure
Substances
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Antigens, CD
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ENG protein, human
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Endoglin
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Platelet Endothelial Cell Adhesion Molecule-1
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Receptors, Cell Surface
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Transforming Growth Factor beta
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Vascular Cell Adhesion Molecule-1