Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene

N Ferrara, K Carver-Moore, H Chen, M Dowd, L Lu… - Nature, 1996 - nature.com
N Ferrara, K Carver-Moore, H Chen, M Dowd, L Lu, KS O'Shea, L Powell-Braxton, KJ Hillan…
Nature, 1996nature.com
ANGIOGENESIS is required for a wide variety of physiological and pathological processes1.
The endothelial cell-specific mitogen vascular endothelial growth factor (VEGF) 2, 3 is a
major mediator of pathological angiogenesis4–6. Also, the expression of VEGF and its two
receptors, Flt-1 and Flk-1/KDR, is related to the formation of blood vessels in mouse and rat
embryos7–10. Mice homozygous for mutations that inactivate either receptor die in utero
between days 8.5 and 9.5 (refs 11, 12). However, ligand (s) other than VEGF might activate …
Abstract
ANGIOGENESIS is required for a wide variety of physiological and pathological processes1. The endothelial cell-specific mitogen vascular endothelial growth factor (VEGF)2,3 is a major mediator of pathological angiogenesis4–6. Also, the expression of VEGF and its two receptors, Flt-1 and Flk-1/KDR, is related to the formation of blood vessels in mouse and rat embryos7–10. Mice homozygous for mutations that inactivate either receptor die in utero between days 8.5 and 9.5 (refs 11,12). However, ligand(s) other than VEGF might activate such receptors13,14. To assess the role of VEGF directly, we disrupted the VEGF gene in embryonic stem cells. Here we report the unexpected finding that loss of a single VEGF allele is lethal in the mouse embryo between days 11 and 12. Angiogenesis and blood-island formation were impaired, resulting in several developmental anomalies. Furthermore, VEGF-null embryonic stem cells exhibit a dramatically reduced ability to form tumours in nude mice.
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