Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
Copyright policy )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.
- University of Toronto Canada
- Lunenfeld-Tanenbaum Research Institute Canada
- Mount Sinai Hospital Canada
- Katholieke Universiteit Leuven Belgium
- Max Planck Society Germany
Vascular Endothelial Growth Factor A, Heterozygote, Lymphokines, Embryo, Nonmammalian, Base Sequence, Vascular Endothelial Growth Factors, Homozygote, Molecular Sequence Data, Endothelial Growth Factors, Embryo, Mammalian, Cell Line, Embryonic and Fetal Development, Culture Techniques, Animals, Blood Vessels, Fetal Death, Alleles, Gene Deletion, DNA Primers
Vascular Endothelial Growth Factor A, Heterozygote, Lymphokines, Embryo, Nonmammalian, Base Sequence, Vascular Endothelial Growth Factors, Homozygote, Molecular Sequence Data, Endothelial Growth Factors, Embryo, Mammalian, Cell Line, Embryonic and Fetal Development, Culture Techniques, Animals, Blood Vessels, Fetal Death, Alleles, Gene Deletion, DNA Primers
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