The studies on the practical application of NOD-sc/d, yc null mice allowing an efficient transplantation of human cells, to human disease models

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1. We have eliminated C57BL/6 genes which originated frolL-2Rγ KO mice and still remained in NOG mice, by further backcross mating to NOD/Shi- scid mice. The reproduction efficacy of NOG mice was almost same to that of NOD/Shi- scid mice. The reproduction efficacy of NOG mice was almost same to that of NOD/Shi- scid mice.2. After intravenous inoculation of human cord blood CD34^+ cells, the NOG mice allowed the extremely higher growth rate of human cells when compared with NOD/Shi-scid mice. In addition, human CD4^+ T and CD8^+ T cells could differentiate in these mice. Human B cells also generated and reproduced human immunoglobulins in NOG mice.3. When HIV-1 was inoculated to PBL-NOG-hu mice, which were inoculated with human PBMC, the significantly high level of HIV-1 p24 gag as well as HIV-1 RNA in plasma and cell-associated HIV-1 DNA were detected, respectively. Simultaneously, the remarkable level of human CD4+ cell depletion was observed.4. In HTLV-1 infection NOG model, two to 3 … More weeks after subcutaneous inoculation of HTLV-1 infected cell lines in the post-auricular region of NOG mice, a visible tumor developed in the site. Almost all cell lines formed a progressively growing large tumor mass with leukemic infiltration of cells in various organs.5. Seven weeks after intravenous inoculation of U266 cells, which were IL-6 dependent human myeloma cell line, to NOG mice, U226 cells massively infiltrated in bone marrow of NOG mice and also invaded into the spiral cord plexus, and finally caused hind leg paralysis, weight loss and distress as observed in human patients.6. NOG mice showed high growth rate of primary human tumor transplantation. When human pancreas tumor cells, i.e. Capan-1 and PANC-1, were inoculated into the mouse spleen, the high metastasis rates in liver were observed in NOG mice but not NOD/Shi- scid mice. These results indicated that NOG mice were extremely useful tools for human disease model.These results indicated that NOG mice were extremely useful tools for human disease model. Less