Defective angiogenesis in mice lacking endoglin.
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.
Li
D Y
DY
Program in Human Molecular Biology and Genetics, Department of Human Genetics, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112-5330, USA. dean.li@hci.utah.edu
Sorensen
L K
LK
Brooke
B S
BS
Urness
L D
LD
Davis
E C
EC
Taylor
D G
DG
Boak
B B
BB
Wendel
D P
DP
D000818:Animals; D015703:Antigens, CD; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002454:Cell Differentiation; D003433:Crosses, Genetic; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology*; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D015017:Yolk Sac / Q000648:ultrastructure
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1