The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility.
Cattelino, Anna ; Liebner, Stefan ; Gallini, Radiosa ; et al. ; - ASI Sponsor
Sep - 2003
ISSN : 0021-9525 ;
journal : The Journal of cell biology

Issue : 6
type: Article Journal

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.

keywords : Actins,Actins: genetics,Actins: metabolism,Animal,Animals,Blood Vessels,Blood Vessels: abnormalities,Blood Vessels: pathology,Blood Vessels: ultrastructure,Capillary Permeability,Capillary Permeability: genetics,Cell Adhesion,Cell Adhesion: genetics,Cell Membrane Permeability,Cell Membrane Permeability: genetics,Cells,Cultured,Cytoskeletal Proteins,Cytoskeletal Proteins: deficiency,Cytoskeletal Proteins: genetics,Cytoskeletal Proteins: metabolism,Cytoskeleton,Cytoskeleton: genetics,Cytoskeleton: pathology,Cytoskeleton: ultrastructure,Desmoplakins,Developmental,Developmental: genetic,Disease Models,Down-Regulation,Down-Regulation: genetics,Electron,Endocardium,Endocardium: abnormalities,Endocardium: pathology,Endocardium: ultrastructure,Endothelium,Fetus,Gene Expression Regulation,Gene Silencing,Gene Silencing: physiology,Genes,Intercellular Junctions,Intercellular Junctions: genetics,Intercellular Junctions: pathology,Intercellular Junctions: ultrastructure,Knockout,Lethal,Lethal: genetics,Mice,Microscopy,Neovascularization,Physiologic,Physiologic: genetics,Trans-Activators,Trans-Activators: deficiency,Trans-Activators: genetics,Vascular,Vascular: abnormalities,Vascular: pathology,Vascular: ultrastructure,beta Catenin