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Science 28 May 1999:
Vol. 284. no. 5419, pp. 1534 - 1537
DOI: 10.1126/science.284.5419.1534
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Reports

Defective Angiogenesis in Mice Lacking Endoglin

Dean Y. Li, 134* Lise K. Sorensen, 5 Benjamin S. Brooke, 134 Lisa D. Urness, 5 Elaine C. Davis, 6 Douglas G. Taylor, 12 Beth B. Boak, 5 Daniel P. Wendel 12

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.

1 Program in Human Molecular Biology and Genetics,
2 Department of Human Genetics,
3 Department of Oncological Sciences,
4 Department of Medicine,
5 Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112-5330, USA.
6 Department of Cell Biology and Neuroscience, University of Texas, Southwestern Medical Center, Dallas, TX 75235-9039, USA.
*   To whom correspondence should be addressed. E-mail: dean.li{at}hci.utah.edu

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Stroke 34, 2483-2488
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Tumor-host interaction mediates the regression of BK virus-induced vascular tumors in mice: involvement of transforming growth factor-{beta}1.
A. Corallini, L. Possati, C. Trabanelli, E. Giraudo, R. Rocchetti, S. Talevi, A. Caputo, F. Bussolino, and G. Barbanti-Brodano (2003)
Carcinogenesis 24, 1435-1444
   Abstract »    Full Text »    PDF »
CD105 prevents apoptosis in hypoxic endothelial cells.
C. Li, R. Issa, P. Kumar, I. N. Hampson, J. M. Lopez-Novoa, C. Bernabeu, and S. Kumar (2003)
J. Cell Sci. 116, 2677-2685
   Abstract »    Full Text »    PDF »
Endoglin Is Not a Major Susceptibility Gene for Intracranial Aneurysm Among Japanese.
H. Onda, H. Kasuya, T. Yoneyama, T. Hori, T. Nakajima, and I. Inoue (2003)
Stroke 34, 1640-1644
   Abstract »    Full Text »    PDF »
CD105 is important for angiogenesis: evidence and potential applications.
S. E. DUFF, C. LI, J. M. GARLAND, and S. KUMAR (2003)
FASEB J 17, 984-992
   Abstract »    Full Text »    PDF »
Vascular morphogenesis: tales of two syndromes.
D. A. Marchuk, S. Srinivasan, T. L. Squire, and J. S. Zawistowski (2003)
Hum. Mol. Genet. 12, R97-112
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Hereditary hemorrhagic telangiectasia: an update on transforming growth factor {beta} signaling in vasculogenesis and angiogenesis.
S. van den Driesche, C. L. Mummery, and C. J.J. Westermann (2003)
Cardiovasc Res 58, 20-31
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Mouse Model for Hereditary Hemorrhagic Telangiectasia Has a Generalized Vascular Abnormality.
E. Torsney, R. Charlton, A. G. Diamond, J. Burn, J. V. Soames, and H. M. Arthur (2003)
Circulation 107, 1653-1657
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Cellular response to hypoxia involves signaling via Smad proteins.
H. Zhang, H. O. Akman, E. L. P. Smith, J. Zhao, J. E. Murphy-Ullrich, and O. A. Batuman (2003)
Blood 101, 2253-2260
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Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels.
B. L. Roman, V. N. Pham, N. D. Lawson, M. Kulik, S. Childs, A. C. Lekven, D. M. Garrity, R. T. Moon, M. C. Fishman, R. J. Lechleider, et al. (2003)
Development 129, 3009-3019
   Abstract »    Full Text »    PDF »
Hedgehog is required for murine yolk sac angiogenesis.
N. Byrd, S. Becker, P. Maye, R. Narasimhaiah, B. St-Jacques, X. Zhang, J. McMahon, A. McMahon, and L. Grabel (2003)
Development 129, 361-372
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A Mutant Receptor Tyrosine Phosphatase, CD148, Causes Defects in Vascular Development.
T. Takahashi, K. Takahashi, P. L. St. John, P. A. Fleming, T. Tomemori, T. Watanabe, D. R. Abrahamson, C. J. Drake, T. Shirasawa, and T. O. Daniel (2003)
Mol. Cell. Biol. 23, 1817-1831
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Transcription Profiling of Platelet-Derived Growth Factor-B-Deficient Mouse Embryos Identifies RGS5 as a Novel Marker for Pericytes and Vascular Smooth Muscle Cells.
C. Bondjers, M. Kalen, M. Hellstrom, S. J. Scheidl, A. Abramsson, O. Renner, P. Lindahl, H. Cho, J. Kehrl, and C. Betsholtz (2003)
Am. J. Pathol. 162, 721-729
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Cerebral Vascular Abnormalities in a Murine Model of Hereditary Hemorrhagic Telangiectasia.
J. Satomi, R. J. Mount;, M. Toporsian, A. D. Paterson, M. C. Wallace, R. V. Harrison, and M. Letarte (2003)
Stroke 34, 783-789
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HEX Acts as a Negative Regulator of Angiogenesis by Modulating the Expression of Angiogenesis-Related Gene in Endothelial Cells In Vitro.
T. Nakagawa, M. Abe, T. Yamazaki, H. Miyashita, H. Niwa, S. Kokubun, and Y. Sato (2003)
Arterioscler Thromb Vasc Biol 23, 231-237
   Abstract »    Full Text »    PDF »


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