Article
- The EMBO Journal (2001) 20, 1663 - 1673
- doi:10.1093/emboj/20.7.1663
Abnormal angiogenesis but intact hematopoietic potential in TGF-
type I receptor-deficient mice
Jonas Larsson1, Marie-José Goumans2, Lottie Jansson Sjöstrand1, Marga A. van Rooijen3, Dorien Ward3, Per Levéen1, Xiufeng Xu1, Peter ten Dijke2, Christine L. Mummery3 and Stefan Karlsson1
- Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine and Department of Medicine, Lund University Hospital, Lund, Sweden
- Netherlands Cancer Institute, Amsterdam, The Netherlands
- Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands
Correspondence to:
Stefan Karlsson, E-mail: Stefan.Karlsson@molmed.lu.se
Received 13 October 2000; Accepted 1 February 2001; Revised 23 January 2001
Abstract
Deletion of the transforming growth factor 
1 (TGF-1) gene in mice has previously suggested that it regulates both hematopoiesis and angiogenesis. To define the function of TGF- more precisely, we inactivated the TGF- type I receptor (TRI) gene by gene targeting. Mice lacking TRI die at midgestation, exhibiting severe defects in vascular development of the yolk sac and placenta, and an absence of circulating red blood cells. However, despite obvious anemia in the TRI-/- yolk sacs, clonogenic assays on yolk sac-derived hematopoietic precursors in vitro revealed that TRI-/- mice exhibit normal hematopoietic potential compared with wild-type and heterozygous siblings. Endothelial cells derived from TRI-deficient embryos show enhanced cell proliferation, improper migratory behavior and impaired fibronectin production in vitro, defects that are associated with the vascular defects seen in vivo. We thus demonstrate here that, while TRI is crucial for the function of TGF- during vascular development and can not be compensated for by the activin receptor-like kinase-1 (ALK-1), functional hematopoiesis and development of hematopoietic progenitors is not dependent on TGF- signaling via TRI.
Keywords:
- endothelial cell,
- hematopoiesis,
- serine,
- signal transduction,
- TGF-,
- threonine kinase receptor
