Notch1 activation in mice causes arteriovenous malformations phenocopied by ephrinB2 and EphB4 mutants.

Genesis : the Journal of Genetics and Development
Luke T KrebsThomas Gridley

Abstract

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.

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Citations

Dec 22, 2011·International Journal of Vascular Medicine·Masahiro Murakami
Oct 15, 2011·Cells, Tissues, Organs·John C ChappellVictoria L Bautch
Aug 7, 2012·Genes & Cancer·Natalie M KoflerJan Kitajewski
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Oct 1, 2013·Cellular and Molecular Life Sciences : CMLS·Deepak AtriMichael Simons
Dec 4, 2014·Proceedings of the National Academy of Sciences of the United States of America·Patrick A MurphyRong A Wang
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Oct 8, 2013·Hematology/oncology Clinics of North America·Angela CioffiRobert G Maki
May 13, 2014·Genesis : the Journal of Genetics and Development·Ju LiuCorrinne G Lobe
Jul 23, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Sonja RothweilerDavid Semela
Dec 10, 2015·BioMed Research International·Ming XuZhiyong Qin
Jan 13, 2015·Annals of Clinical and Translational Neurology·Lorelei D ShoemakerSteven D Chang
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Mar 17, 2012·Developmental Cell·Bruno LarrivéeAnne Eichmann
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Jan 16, 2021·Angiogenesis·Leah J Greenspan, Brant M Weinstein
Feb 26, 2021·Clinical Genetics·Maian RoifmanDavid Chitayat

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