NOD/SCID/γcnull mouse: an excellent recipient mouse model for engraftment of human cells

DOI PDF 被引用文献265件
  • Mamoru Ito
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Hidefumi Hiramatsu
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Kimio Kobayashi
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Kazutomo Suzue
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Mariko Kawahata
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Kyoji Hioki
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Yoshito Ueyama
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Yoshio Koyanagi
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Kazuo Sugamura
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Kohichiro Tsuji
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Toshio Heike
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
  • Tatsutoshi Nakahata
    From the Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University; Department of Parasitology, School of Medicine, Gunma University; Department of Pathology, School of Medicine, Tokai University; Departments of Virology and Immunology, Graduate School of Medicine, Tohoku University; Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.

抄録

<jats:title>Abstract</jats:title><jats:p>To establish a more appropriate animal recipient for xenotransplantation, NOD/SCID/γcnull mice double homozygous for the severe combined immunodeficiency (SCID) mutation and interleukin-2Rγ (IL-2Rγ) allelic mutation (γcnull) were generated by 8 backcross matings of C57BL/6J-γcnull mice and NOD/Shi-scidmice. When human CD34+ cells from umbilical cord blood were transplanted into this strain, the engraftment rate in the peripheral circulation, spleen, and bone marrow were significantly higher than that in NOD/Shi-scid mice treated with anti-asialo GM1 antibody or in the β2-microglobulin–deficient NOD/LtSz-scid (NOD/SCID/β2mnull) mice, which were as completely defective in NK cell activity as NOD/SCID/γcnull mice. The same high engraftment rate of human mature cells was observed in ascites when peripheral blood mononuclear cells were intraperitoneally transferred. In addition to the high engraftment rate, multilineage cell differentiation was also observed. Further, even 1 × 102 CD34+ cells could grow and differentiate in this strain. These results suggest that NOD/SCID/γcnull mice were superior animal recipients for xenotransplantation and were especially valuable for human stem cell assay. To elucidate the mechanisms involved in the superior engraftment rate in NOD/SCID/γcnull mice, cytokine production of spleen cells stimulated with Listeria monocytogenesantigens was compared among these 3 strains of mice. The interferon-γ production from dendritic cells from the NOD/SCID/γcnull mouse spleen was significantly suppressed in comparison with findings in 2 other strains of mice. It is suggested that multiple immunological dysfunctions, including cytokine production capability, in addition to functional incompetence of T, B, and NK cells, may lead to the high engraftment levels of xenograft in NOD/SCID/γcnull mice.</jats:p>

収録刊行物

  • Blood

    Blood 100 (9), 3175-3182, 2002-11-01

    American Society of Hematology

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