Protective Effects of Transgenic Human Endothelial Protein C Receptor Expression in Murine Models of Transplantation
KFE Lee, B Lu, JC Roussel, LJ Murray-Segal, EJ Salvaris, SJ Hodgkinson, BM Hall, AJF d'Apice, PJ Cowan, H Gock
American Journal of Transplantation | WILEY-BLACKWELL | Published : 2012
Thrombosis and inflammation are major obstacles to successful pig-to-human solid organ xenotransplantation. A potential solution is genetic modification of the donor pig to overexpress molecules such as the endothelial protein C receptor (EPCR), which has anticoagulant, anti-inflammatory and cytoprotective signaling properties. Transgenic mice expressing human EPCR (hEPCR) were generated and characterized to test this approach. hEPCR was expressed widely and its compatibility with the mouse protein C pathway was evident from the anticoagulant phenotype of the transgenic mice, which exhibited a prolonged tail bleeding time and resistance to collagen-induced thrombosis. hEPCR mice were protect..View full abstract
This work was supported by the NHMRC. K. F. E. L. was the recipient of an NHMRC postgraduate research scholarship. H. G. was the recipient of The Royal Australasian College of Physicians' Jacquot Research Establishment Award and an award from the Research Endowment Fund of St Vincent's Hospital, Melbourne. We would like to thank Professor Harshal Nandurkar for helpful comments on the manuscript. We also thank Helen Barlow and the staff of the St. Vincent's Hospital Bioresources Centre for assistance in the generation and maintenance of transgenic mice.this study was funded in part by the Australian National Health and Medical Research Council (NHMRC).