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Title: Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
Authors: Carmeliet, Peter ×
Ferreira, V
Breier, G
Pollefeyt, S
Kieckens, Magdalena
Gertsenstein, M
Fahrig, M
Vandenhoeck, Ann
Harpal, K
Eberhardt, C
Declercq, C
Pawling, J
Moons, Lieve
Collen, Desire
Risau, W
Nagy, A #
Issue Date: Apr-1996
Series Title: Nature vol:380 issue:6573 pages:435-9
Abstract: 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.
URI: 
ISSN: 0028-0836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Animal Physiology and Neurobiology Section - miscellaneous
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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