title: The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility.
abstract: Using the Cre/loxP system we conditionally inactivated beta-catenin in endothelial cells. We found that early phases of vasculogenesis and angiogenesis were not affected in mutant embryos; however, vascular patterning in the head, vitelline, umbilical vessels, and the placenta was altered. In addition, in many regions, the vascular lumen was irregular with the formation of lacunae at bifurcations, vessels were frequently hemorrhagic, and fluid extravasation in the pericardial cavity was observed. Cultured beta-catenin -/- endothelial cells showed a different organization of intercellular junctions with a decrease in alpha-catenin in favor of desmoplakin and marked changes in actin cytoskeleton. These changes paralleled a decrease in cell-cell adhesion strength and an increase in paracellular permeability. We conclude that in vivo, the absence of beta-catenin significantly reduces the capacity of endothelial cells to maintain intercellular contacts. This may become more marked when the vessels are exposed to high or turbulent flow, such as at bifurcations or in the beating heart, leading to fluid leakage or hemorrhages.
authors.affiliation: FIRC Institute of Molecular Oncology, 16-20139, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Cattelino
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebner
authors.forename: Radiosa
authors.initials: R
authors.lastname: Gallini
authors.forename: Adriana
authors.initials: A
authors.lastname: Zanetti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Balconi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corsi
authors.forename: Paolo
authors.initials: P
authors.lastname: Bianco
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.forename: Robert
authors.initials: R
authors.lastname: Moore
authors.forename: Boussadia
authors.initials: B
authors.lastname: Oreda
authors.forename: Rolf
authors.initials: R
authors.lastname: Kemler
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000002:abnormalities* / Q000473:pathology / Q000648:ultrastructure; D002199:Capillary Permeability / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D002463:Cell Membrane Permeability / Q000235:genetics; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D051180:Desmoplakins; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D004699:Endocardium / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000002:abnormalities* / Q000473:pathology / Q000648:ultrastructure; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D020868:Gene Silencing / Q000502:physiology; D005804:Genes, Lethal / Q000235:genetics; D007365:Intercellular Junctions / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018919:Neovascularization, Physiologic / Q000235:genetics*; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D051176:beta Catenin
chemical_list: D000199:Actins; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495295:Dsp protein, mouse; D015534:Trans-Activators; D051176:beta Catenin