Polymorphic SIRPA is the genetic determinant for nod-based mouse lines to achieve efficient human cell engraftment

Abstract

To evaluate stem cell potential of human cells in xenotransplant models, a variety of immunodeficient mouse lines have been developed. Depletion of lymphoid cells including T, B and NK cells by introducing with Il2rgnull, and SCID or RAGnull mutations is necessary to avoid rejection of human cells in these models. Interestingly, in mice having these immunodeficiencies, the NOD strain shows even better engraftment of human cells as compared to C57BL/6 or Balb/c strains. Recently, we found that in xenograft rejection, the innate phagocytic reaction of mouse macrophages could occur because murine signal regulatory protein alpha (mSIRPA) on macrophages cannot bind to human CD47 (hCD47).