Endoglin, an ancillary TGF beta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development

Endoglin (CD105) is expressed on the surface of endothelial and haematopoie tic cells in mammals and binds TGF beta isoforms 1 and 3 in combination wit h the signaling complex of TGF beta receptors types I and II. Endoglin expr ession increases during angiogenesis, wound healing, and inflammation, all of which are associated with TGF beta signaling and alterations in vascular structure. The importance of endoglin for normal vascular architecture is further indicated by the association of mutations in the endoglin gene with the inherited disorder Hereditary Haemorrhagic Telangiectasia Type 1 (HHT1 ), a disease characterised by bleeding from vascular malformations. In orde r to study the role of endoglin in vivo in more detail and to work toward d eveloping an animal model of HHT1, we have derived mice that carry a target ed nonsense mutation in the endoglin gene. Studies on these mice have revea led that endoglin is essential for early development. Embryos homozygous fo r the endoglin mutation fail to progress beyond 10.5 days postcoitum and fa il to form mature blood vessels in the yolk sac. This phenotype is remarkab ly similar to that of the TGF beta 1 and the TGF beta receptor II knockout mice, indicating that endoglin is needed in vivo for TGF beta 1 signaling d uring extraembryonic vascular development. In addition, we have observed ca rdiac defects in homozygous endoglin-deficient embryos, suggesting endoglin also plays a role in cardiogenesis. We anticipate that heterozygous mice w ill ultimately serve as a useful disease model for HHT1, as some individual s have dilated and fragile blood vessels similar to vascular malformations seen in HHT patients, (C) 2000 Academic Press.