Over the past 15 years, there has been an explosion of new understanding of the molecular basis of thrombosis based on murine models. One of the major basis for this increase in use of murine models has been the ability to make transgenic and knockout animals of many of the proteins involved in the complex process by which thrombi develop both under physiological and pathological conditions. Furthermore, given the short time to reproduce and the ability to cross multiple, genetically-modified murine lines, the influence of one component of coagulation on another can finally be tested. Mice also have their drawbacks in that systems for studying thrombus development have been slow to develop. Over this past year, my group has established a carotid thrombus model at the combined Children's Hospital of Philadelphia/University of Pennsylvania (CHOP/PENN) campus, with much useful information already coming from that model. We have also begun to teach our CHOP/PENN colleagues how to study their animal models using this approach as well. But at the same time, we have come to realize that much more useful information can come from a recently developed, more sophisticated system that allows detailed analysis of the developing thrombus. Dr. Bruce Furie at Harvard University has developed such a system and has provided us with preliminary data and helped us with obtaining a complete price quote for his system, which involves laser-induced ablation of a single cremaster muscle microartery's endothelial cell. The developing thrombus is followed using a state-of-the-art confocal, widefield scanning microscope and then stored for quantitative data analysis of the developed thrombus. This system will become the central component of a Murine Thrombosis Model Core that will enable the entire body of NIH-supported thrombosis investigators on the CHOP/PENN campus to study thrombus development in a sophisticated fashion to provide important insights into their specific NIH-supported reserach efforts. This application describes how this system will be beneficial to five specific NIH-supported laboratories on the CHOP/PENN campus, with the anticipation that once established that additional investigators in this campus will be able to use this system as well.
