The A1 domain of von Willebrand factor plays a crucial role in hemostasis and thrombosis, as it initiates platelet adhesion at sites of arterial injury. Therefore, modulation of the activation of this domain is of interest for antithrombotic therapies. However, in vivo testing of these therapies is difficult, as the structure of this domain in mouse von Willebrand factor differs significantly from that of human. This technology describes development of a mouse model with a humanized A1 domain, capable of thrombus formation only in the presence of human platelets. This transgenic mouse model has the potential to serve as a cost-effective model for the development and testing of potential therapies for clotting disorders and diseases associated with thrombosis.
Through replacement of the majority of the murine A1 domain of von Willebrand factor with its human counterpart, this animal model supports human but not mouse platelet-mediated thrombosis. This biological platform allows for the controlled testing of antithrombotic therapies on human von Willebrand factor activity, without influence from the mouse clotting cascade. This model may help to expedite drug development and screening by serving as a pharmacodynamic and functional response biomarker for antithrombotic agents, and may serve to better predict the clinical efficacy of these agents.
This transgenic mouse model has been validated through in vivo testing of multiple anti-platelet therapies, including abciximab, eptifibatide, and tirofiban.
Patent Pending (WO/2008/005290)
Tech Ventures Reference: IR CU12307