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Notch1 activation in mice causes arteriovenous malformations phenocopied by ephrinB2 and EphB4 mutants
Author(s) -
Krebs Luke T.,
Starling Christa,
Chervonsky Alexander V.,
Gridley Thomas
Publication year - 2010
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20599
Subject(s) - phenocopy , mutant , biology , embryo , microbiology and biotechnology , notch signaling pathway , embryonic stem cell , gain of function , loss function , gene , function (biology) , signal transduction , phenotype , genetics
Notch signaling is essential for embryonic vascular development in mammals and other vertebrates. Here we show that mouse embryos with conditional activation of the Notch1 gene in endothelial cells ( Notch1 gain of function embryos) exhibit defects in vascular remodeling increased diameter of the dorsal aortae, and form arteriovenous malformations. Conversely, embryos with either constitutive or endothelial cell‐specific Notch1 gene deletion also have vascular defects, but exhibit decreased diameter of the dorsal aortae and form arteriovenous malformations distinctly different from the Notch1 gain of function mutants. Surprisingly, embryos homozygous for mutations of the ephrinB/EphB pathway genes Efnb2 and Ephb4 exhibit vascular defects and arteriovenous malformations that phenocopy the Notch1 gain of function mutants. These results suggest that formation of arteriovenous malformations in Notch1 gain of function mutants and ephrinB/EphB pathway loss of function mutant embryos occurs by different mechanisms. genesis 48:146–150, 2010. © 2010 Wiley‐Liss, Inc.