DEVELOPMENT OF A MOUSE AORTIC TRANSPLANT MODEL OF CHRONIC REJECTION

Chronic rejection is the most common cause of late graft failure after solid organ transplantation. A model of chronic rejection, the rat ao rtic allograft, has histologic features that parallel those in the ves sels of human transplanted organs. However, the molecular tools requir ed to dissect the immunology of chronic rejection are unavailable in t he rat. We developed aortic transplantation in the mouse as a new mode l of chronic rejection. This will allow the use of the diversity of re combinant cytokines and monoclonal antibodies available for the mouse and its well-defined genetics to investigate chronic rejection in grea ter detail. We describe the perioperative care and surgical technique for the model in which a 1 cm segment of donor thoracic aorta was used to replace a section of recipient abdominal aorta below the renal art eries and above the aortic bifurcation, Mortality rates were initially high (70%) due to thrombosis and shock, Changes in technique and oper ator facility resulted in a high rate of success (75%), After 192 oper ations, the current success rate is >80%. Mice free from complications at 12 hrs postop had indefinite survival, and after 2 months the typi cal vascular lesion of chronic rejection was present. This new model o f chronic rejection will be a valuable tool to study the molecular imm unology and genetics of chronic rejection. (C) 1995 Wiley-Liss, Inc.