PMID- 8602241
OWN - NLM
STAT- MEDLINE
DCOM- 19960503
LR  - 20240109
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 380
IP  - 6573
DP  - 1996 Apr 4
TI  - Abnormal blood vessel development and lethality in embryos lacking a single VEGF 
      allele.
PG  - 435-9
AB  - 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.
FAU - Carmeliet, P
AU  - Carmeliet P
AD  - Center for Transgene Technology and Gene Therapy, Flanders Interuniversity 
      Institute for Biotechnology, Leuven, Belgium.
FAU - Ferreira, V
AU  - Ferreira V
FAU - Breier, G
AU  - Breier G
FAU - Pollefeyt, S
AU  - Pollefeyt S
FAU - Kieckens, L
AU  - Kieckens L
FAU - Gertsenstein, M
AU  - Gertsenstein M
FAU - Fahrig, M
AU  - Fahrig M
FAU - Vandenhoeck, A
AU  - Vandenhoeck A
FAU - Harpal, K
AU  - Harpal K
FAU - Eberhardt, C
AU  - Eberhardt C
FAU - Declercq, C
AU  - Declercq C
FAU - Pawling, J
AU  - Pawling J
FAU - Moons, L
AU  - Moons L
FAU - Collen, D
AU  - Collen D
FAU - Risau, W
AU  - Risau W
FAU - Nagy, A
AU  - Nagy A
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (DNA Primers)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Lymphokines)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Base Sequence
MH  - Blood Vessels/*abnormalities/embryology
MH  - Cell Line
MH  - Culture Techniques
MH  - DNA Primers
MH  - Embryo, Mammalian/*abnormalities/blood supply
MH  - *Embryo, Nonmammalian
MH  - Embryonic and Fetal Development/genetics/physiology
MH  - Endothelial Growth Factors/deficiency/*genetics/*physiology
MH  - Fetal Death/genetics
MH  - Gene Deletion
MH  - Heterozygote
MH  - Homozygote
MH  - Lymphokines/deficiency/*genetics/*physiology
MH  - Molecular Sequence Data
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1996/04/04 00:00
MHDA- 1996/04/04 00:01
CRDT- 1996/04/04 00:00
PHST- 1996/04/04 00:00 [pubmed]
PHST- 1996/04/04 00:01 [medline]
PHST- 1996/04/04 00:00 [entrez]
AID - 10.1038/380435a0 [doi]
PST - ppublish
SO  - Nature. 1996 Apr 4;380(6573):435-9. doi: 10.1038/380435a0.