Antibody mediated rejection (AMR) is main barrier to long term renal graft survival and mouse model is important to understand the mechanisms of AMR and exploring novel therapeutic strategies. Current mouse renal AMR models were established by priming recipients to donor skin grafts over 7 days prior to kidney transplant. This model in our hand borders hyper acute rejection and cannot ideally model clinical acute AMR. In this study, we investigated the regulatory role of skin priming time within 7 days in the outcomes of subsequent skin-matched renal grafts. We found 4-day skin priming can guarantee recipients develop acute renal allograft AMR mixed with mild cellular rejection, renal grafts survived mean 6.4±2.1 days, characterized by glomerulitis, peritubular capillary (PTC) dilation and capillaritis, deposition of IgG and C3d in PTC but less prevalence of microthrombus in histological changes, rendering the model to better simulate clinical scenario. The improved model was also featured by detectable DSAs only after kidney transplant, implying its more approach to de novo DSA. We also testified renal allograft AMR model can be constructed using the most common lab mice of C57BL/6 and Balb/c, featured by prolonged renal graft survival time of mean 14.4±5.0 days. Finally, we proved donor matched skin challenge after kidney transplant hardly affected de novo DSA development. These findings facilitated establishment of improved mouse renal allograft AMR models and promote associated studies.

CITATION INFORMATION: Zhao D., Liao T., Li S., Zhou J., Han F., Dong Y., Sun Q. Improved Mouse Renal Transplantation Model Mimicking Clinical Antibody Mediated Rejection Am J Transplant. 2017;17 (suppl 3).

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