| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
We have previously developed C.B-17 scid mice whose circulating red blood cells (RBCs) had been substituted with RBCs of other animal species. This innovative animal model system greatly facilitated in vivo research for erythroparasitic protozoa that are in nature not infectious to mice. However, the substitution of C.B-17 scid mice with RBCs of some animal species, such as humans and horses, is proved to be very difficult, because of rapid clearance of RBCs transfused in C.B-17 scid mice. In recent years, attempts have been made to develop better SCID mice by changing the genetic background from C.B-17 into the other mice strains, and the NOD-scid mice (the non-obese diabetic mice having the scid mutation) were reported to have significantly improved hematopoietic xeno-transplant acceptability. In the present study, therefore, we examined acceptability of xenogeneic RBCs in NOD/shi-scid in comparison to C.B-17 scid. Clearance tests with fluorescent labeled RBCs of human, dog, horse and cattle showed that life spans of all these RBCs were significantly longer in NOD-scid than in C.B-17 scid mice. In addition, the ability of xeno-RBCs clearance in C.B-17 scid mice was greatly enhanced by some factors, such as optimistic infections, macrophage activating stimuli and aging, whereas such enhancement was poorly observed in NOD-scid mice. These lines of evidence collectively suggest that NOD-scid mice serve as more suitable SCID mice for preparation of the RBC-substitution model than C.B-17 scid. However, NOD-scid mice were less capable of eliminating mouse RBCs upon administration of anti-mouse RBC antibodies, which was effectively used in C.B-17 scid mice to assist rapid RBC-substitution. We were able to demonstrated that NOD-scid mice can easily substituted with human RBCs, and that the human RBC-substituted SCID mice served as an exellent tool for isolation of parasites from a human babesiosis case, which was found for the first time in Japan.
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