This Article Full Text Full Text (PDF) All Versions of this Article: 107/12/1653    most recent 01.CIR.0000058170.92267.00v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Torsney, E. Articles by Arthur, H. M. Search for Related Content PubMed PubMed Citation Articles by Torsney, E. Articles by Arthur, H. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Related Collections Angiogenesis Animal models of human disease Smooth muscle proliferation and differentiation

(Circulation. 2003;107:1653.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Mouse Model for Hereditary Hemorrhagic Telangiectasia Has a Generalized Vascular Abnormality

Evelyn Torsney, PhD; Richard Charlton, PhD; Austin G. Diamond, PhD; John Burn, MD; James V. Soames, PhD; Helen M. Arthur, PhD

From the Institute of Human Genetics, International Centre for Life (E.T., J.B., H.M.A.), Microbiology and Immunology (A.G.D.), and Oral Pathology, University of Newcastle upon Tyne (J.V.S.); and Histopathology, Freeman Hospital (R.C.), Newcastle upon Tyne, UK.

Correspondence to Dr Helen M. Arthur, Institute of Human Genetics, International Centre for Life, University of Newcastle upon Tyne, NE1 3BZ, UK. E-mail helen.arthur{at}ncl.ac.uk

Background— Mutations in endoglin or activin like kinase-1, both involved in the endothelial transforming growth factor-ß 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.

Methods and 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.

Key Words: vasculature • angiogenesis • hemorrhage • inflammation

This article has been cited by other articles:

				S. O. Park, Y. J. Lee, T. Seki, K.-H. Hong, N. Fliess, Z. Jiang, A. Park, X. Wu, V. Kaartinen, B. L. Roman, et al. ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2 Blood, January 15, 2008; 111(2): 633 - 642. [Abstract] [Full Text] [PDF]

				D. Liu, J. Wang, B. Kinzel, M. Mueller, X. Mao, R. Valdez, Y. Liu, and E. Li Dosage-dependent requirement of BMP type II receptor for maintenance of vascular integrity Blood, September 1, 2007; 110(5): 1502 - 1510. [Abstract] [Full Text] [PDF]

				A. Fernandez-L, F. Sanz-Rodriguez, F. J. Blanco, C. Bernabeu, and L. M. Botella Hereditary Hemorrhagic Telangiectasia, a Vascular Dysplasia Affecting the TGF-{beta} Signaling Pathway. Clin. Med. Res., March 1, 2006; 4(1): 66 - 78. [Abstract] [Full Text] [PDF]

				A. Armulik, A. Abramsson, and C. Betsholtz Endothelial/Pericyte Interactions Circ. Res., September 16, 2005; 97(6): 512 - 523. [Abstract] [Full Text] [PDF]

				F. Lebrin, M. Deckers, P. Bertolino, and P. ten Dijke TGF-{beta} receptor function in the endothelium Cardiovasc Res, February 15, 2005; 65(3): 599 - 608. [Abstract] [Full Text] [PDF]

				R. L. C. Carvalho, L. Jonker, M.-J. Goumans, J. Larsson, P. Bouwman, S. Karlsson, P. t. Dijke, H. M. Arthur, and C. L. Mummery Defective paracrine signalling by TGF{beta} in yolk sac vasculature of endoglin mutant mice: a paradigm for hereditary haemorrhagic telangiectasia Development, December 15, 2004; 131(24): 6237 - 6247. [Abstract] [Full Text] [PDF]

				A Karabegovic, M Shinawi, U Cymerman, and M Letarte No live individual homozygous for a novel endoglin mutation was found in a consanguineous Arab family with hereditary haemorrhagic telangiectasia J. Med. Genet., November 1, 2004; 41(11): e119 - e119. [Full Text] [PDF]

				J.-C. Tille and M.S. Pepper Hereditary Vascular Anomalies: New Insights Into Their Pathogenesis Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1578 - 1590. [Abstract] [Full Text] [PDF]

				T. Seki, J. Yun, and S. P. Oh Arterial Endothelium-Specific Activin Receptor-Like Kinase 1 Expression Suggests Its Role in Arterialization and Vascular Remodeling Circ. Res., October 3, 2003; 93(7): 682 - 689. [Abstract] [Full Text] [PDF]