Mouse model for hereditary hemorrhagic telangiectasia has a generalized vascular abnormality.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
These findings have relevance to our understanding of the molecular basis of vascular integrity in a wide range of diseases.
Torsney
Evelyn
E
Institute of Human Genetics, International Centre for Life, University of Newcastle upon Tyne, NE1 3BZ, UK.
Charlton
Richard
R
Diamond
Austin G
AG
Burn
John
J
Soames
James V
JV
Arthur
Helen M
HM
D000818:Animals; D015703:Antigens, CD; D001808:Blood Vessels / Q000002:abnormalities* / Q000473:pathology; D020405:Dermis / Q000098:blood supply; D000071063:Endoglin; D017353:Gene Deletion; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D011956:Receptors, Cell Surface; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1