Project Details
Projekt
Contribution of the Tie/Angiopoietin receptor/ligand system to growth, morphology and function of blood vessels in adult mice
Applicant
Dr. Urban Deutsch
Subject Area
Pathology
Term
from 2001 to 2010
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5347773
The Tie/Angiopoietin receptor/ligand system is involved in vascular remodelling and sprouting as well as in recruitment of mesenchymal cells and thereby contributes to the establishment and maintenance of a functionally intact circulatory system. By their capacity to conversely modulate the interaction of endothelial cells with their perivascular support cells Angiopoietin-1 and -2 are expected to play important roles in various settings of pathological alterations such as vascular changes in growing tumors, during edema formation in inflammatory diseases and in various retinopathies. In the past few years, we have successfully set up a binary system for endothelial cell-specific tetracycline-inducible gene expression in transgenic mice that allows for regulated expression of responder genes in all blood vessels of the developing mouse embryo and in at least a substantial portion of vessels in the adult organism. We will use this system for the inducible expression of Angiopoietin-1 and -2 as well as the orphan receptor Tie-1 in the endothelia of transgenic mice. This will allow to test for functional consequences of endothelial overexpression of the Angiopoietins and the Tie-1 receptor and to dissect cellular as well as molecular changes in the blood vessel wall. Furthermore, induced overexpression might hint at ways to counteract the upregulation of a given Angiopoietin in a pathological setting aiming at possible therapeutic usefulness. In addition, we will attempt to functionally rescue the Ang-2 and Tie-1 null phenotypes by inducible expression of Ang-2 and Tie-1.
DFG Programme
Priority Programmes
International Connection
Switzerland
