Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep27186
Title: Flt1/VEGFR1 heterozygosity causes transient embryonic edema
Authors: Otowa, Y
Moriwaki, K
Sano, K
Shirakabe, M
Yonemura, S
Shibuya, M
Rossant, J
Suda, T 
Kakeji, Y
Hirashima, M
Keywords: Flt1 protein, mouse
Kdr protein, mouse
Ppp1r13b protein, mouse
signal transducing adaptor protein
vascular endothelial growth factor A, mouse
vasculotropin A
vasculotropin receptor 1
vasculotropin receptor 2
animal
capillary permeability
cell membrane
edema
embryo development
endothelium cell
genetic heterogeneity
genetics
metabolism
mouse
mutation
nuchal translucency measurement
phosphorylation
Adaptor Proteins, Signal Transducing
Animals
Capillary Permeability
Cell Membrane
Edema
Embryonic Development
Endothelial Cells
Genetic Heterogeneity
Mice
Mutation
Nuchal Translucency Measurement
Phosphorylation
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Otowa, Y, Moriwaki, K, Sano, K, Shirakabe, M, Yonemura, S, Shibuya, M, Rossant, J, Suda, T, Kakeji, Y, Hirashima, M (2016). Flt1/VEGFR1 heterozygosity causes transient embryonic edema. Scientific Reports 6 : 27186. ScholarBank@NUS Repository. https://doi.org/10.1038/srep27186
Rights: Attribution 4.0 International
Abstract: Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that Flt1 heterozygous (Flt1 +/-) mouse embryos grow up to adult without life-threatening abnormalities but exhibit a transient embryonic edema around the nuchal and back regions, which is reminiscent of increased nuchal translucency in human fetuses. Vascular permeability is enhanced and an intricate infolding of the plasma membrane and huge vesicle-like structures are seen in Flt1 +/- capillary endothelial cells. Flk1 tyrosine phosphorylation is elevated in Flt1 +/- embryos, but Flk1 heterozygosity does not suppress embryonic edema caused by Flt1 heterozygosity. When Flt1 mutants are crossed with Aspp1 -/- mice which exhibit a transient embryonic edema with delayed formation and dysfunction of lymphatic vessels, only 5.7% of Flt1 +/-; Aspp1 -/- mice survive, compared to expected ratio (25%). Our results demonstrate that Flt1 heterozygosity causes a transient embryonic edema and can be a risk factor for embryonic lethality in combination with other mutations causing non-lethal vascular phenotype.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/182466
ISSN: 2045-2322
DOI: 10.1038/srep27186
Rights: Attribution 4.0 International
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