Cardiovascular Failure in Mouse Embryos Deficient in VEGF Receptor-3

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Science  30 Oct 1998:
Vol. 282, Issue 5390, pp. 946-949
DOI: 10.1126/science.282.5390.946

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Vascular endothelial growth factor (VEGF) is a key regulator of blood vessel development in embryos and angiogenesis in adult tissues. Unlike VEGF, the related VEGF-C stimulates the growth of lymphatic vessels through its specific lymphatic endothelial receptor VEGFR-3. Here it is shown that targeted inactivation of the gene encoding VEGFR-3 resulted in defective blood vessel development in early mouse embryos. Vasculogenesis and angiogenesis occurred, but large vessels became abnormally organized with defective lumens, leading to fluid accumulation in the pericardial cavity and cardiovascular failure at embryonic day 9.5. Thus, VEGFR-3 has an essential role in the development of the embryonic cardiovascular system before the emergence of the lymphatic vessels.

  • * These authors contributed equally to this work.

  • Present address: Sunnybrook Health Science Centre, Division of Cancer Biology, S Wing Research Building, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada.

  • Deceased.

  • § To whom correspondence should be addressed. E-mail: Kari.Alitalo{at}Helsinki.FI

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