| Budget Amount *help |
¥3,270,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2009: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research 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 Il2rg^null, and SCID or RAG^null 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 B6 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). However, NOD-specific polymorphism of mSIRPA allows NOD-type SIRPA to bind hCD47, resulting in inhibition of phagocytic reaction against human cells in this strain at least in vitro. Here, we have established a new immunodeficient BRGS mouse line, B6. Rag2^nullIl2rg^null mice with NOD-type Sirpa. The BRGS strain showed efficient engraftment of human hematopoietic stem cells comparable to NOD-Rag1^nullIl2rg^nullstrain. BRGS strain should be very useful in future xenotransplant experiments of human stem cells.
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