Mouse model for hereditary hemorrhagic telangiectasia has a generalized vascular abnormality

Mutations in endoglin or activin like kinase-1, both involved in the endothelial transforming growth factor-beta signaling pathway, cause the autosomal dominant bleeding disorder hereditary hemorrhagic telangiectasia. We and others have reported mouse models for this disease that share the character...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2003-04, Vol.107 (12), p.1653-1657
Main Authors: TORSNEY, Evelyn, CHARLTON, Richard, DIAMOND, Austin G, BURN, John, SOAMES, James V, ARTHUR, Helen M
Format: Article
Language:English
Subjects:
Animals
Antigens, CD
Biological and medical sciences
Blood and lymphatic vessels
Blood Vessels - abnormalities
Blood Vessels - pathology
Cardiology. Vascular system
Dermis - blood supply
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Endoglin
Gene Deletion
Immunohistochemistry
Medical sciences
Mice
Mice, Mutant Strains
Phenotype
Receptors, Cell Surface
Telangiectasia, Hereditary Hemorrhagic - pathology
Vascular Cell Adhesion Molecule-1 - genetics
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Summary:Mutations in endoglin or activin like kinase-1, both involved in the endothelial transforming growth factor-beta signaling pathway, cause the autosomal dominant bleeding disorder hereditary hemorrhagic telangiectasia. We and others have reported mouse models for this disease that share the characteristic phenotype of dilated vessels and sporadic hemorrhage. The reasons for the variable phenotype in hereditary hemorrhagic telangiectasia are not understood. After a detailed immunohistochemical analysis of 129/Ola mice, which are heterozygous for a targeted deletion in the endoglin gene, we observed intrinsic abnormalities in the vascular walls throughout the cutaneous vasculature. Postcapillary venules were dilated, and up to 70% of the vascular wall had no smooth muscle cells. The supporting layers of collagens and elastin were irregular, with thin areas, adding to the fragility of these vessels. A variable hemorrhagic phenotype was observed in which local bleeding is associated not only with fragile vessels but also with regions of inflammation. These findings have relevance to our understanding of the molecular basis of vascular integrity in a wide range of diseases.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.cir.0000058170.92267.00