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Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele.

The endothelial cell-specific vascular endothelial growth factor (VEGF) and its cellular receptors Flt-1 and Flk-1 have been implicated in the formation of the embryonic vasculature. This is suggested by their colocalized expression during embryogenesis and the impaired vessel formation in Flk-1 and Flt-1 deficient embryos. However, because Flt-1 also binds placental growth factor, a VEGF homologue, the precise role of VEGF was unknown. Here we report that formation of blood vessels was abnormal, but not abolished, in heterozygous VEGF-deficient (VEGF+/-) embryos, generated by aggregation of embryonic stem (ES) cells with tetraploid embryos (T-ES) and even more impaired in homozygous VEGF-deficient (VEGF-/-) T-ES embryos, resulting in death at mid-gestation. Similar phenotypes were observed in F1-VEGF+/- embryos, generated by germline transmission. We believe that this heterozygous lethal phenotype, which differs from the homozygous lethality in VEGF-receptor-deficient embryos, is unprecedented for a targeted autosomal gene inactivation, and is indicative of a tight dose-dependent regulation of embryonic vessel development by VEGF.

Pubmed ID: 8602241

Authors

  • Carmeliet P
  • Ferreira V
  • Breier G
  • Pollefeyt S
  • Kieckens L
  • Gertsenstein M
  • Fahrig M
  • Vandenhoeck A
  • Harpal K
  • Eberhardt C
  • Declercq C
  • Pawling J
  • Moons L
  • Collen D
  • Risau W
  • Nagy A

Journal

Nature

Publication Data

April 4, 1996

Associated Grants

None

Mesh Terms

  • Alleles
  • Animals
  • Base Sequence
  • Blood Vessels
  • Cell Line
  • Culture Techniques
  • DNA Primers
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Embryonic and Fetal Development
  • Endothelial Growth Factors
  • Fetal Death
  • Gene Deletion
  • Heterozygote
  • Homozygote
  • Lymphokines
  • Molecular Sequence Data
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors