1. Generation and Characterization of Severe Combined Immunodeficiency Rats
- Author
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Jun-ichiro Yomoda, Jun Hirose, Junya Kobayashi, Asato Tachibana, Takashi Kuramoto, Kazuto Yoshimi, Ami Yanagi, Akiko Takizawa, Takeshi Watanabe, Koji Tanabe, Yayoi Kunihiro, Chise Tateno, Saeko Ishida, Shiho Morimoto, Tomoji Mashimo, Birger Voigt, Tadao Serikawa, Hiroshi Hiai, and Kenshi Komatsu
- Subjects
Pluripotent Stem Cells ,Xenotransplantation ,medicine.medical_treatment ,Lymphocyte ,Transplantation, Heterologous ,DNA-Activated Protein Kinase ,Mice, SCID ,Biology ,Rats, Mutant Strains ,General Biochemistry, Genetics and Molecular Biology ,Gene Knockout Techniques ,Mice ,medicine ,Animals ,Humans ,lcsh:QH301-705.5 ,Immunodeficiency ,Severe combined immunodeficiency ,PRKDC Gene ,medicine.disease ,Phenotype ,Rats ,Transplantation ,Disease Models, Animal ,medicine.anatomical_structure ,lcsh:Biology (General) ,Immunology ,Severe Combined Immunodeficiency ,Stem cell ,Interleukin Receptor Common gamma Subunit - Abstract
Severe combined immunodeficiency (SCID) mice, the most widely used animal model of DNA-PKcs (Prkdc) deficiency, have contributed enormously to our understanding of immunodeficiency, lymphocyte development, and DNA-repair mechanisms, and they are ideal hosts for allogeneic and xenogeneic tissue transplantation. Here, we use zinc-finger nucleases to generate rats that lack either the Prkdc gene (SCID) or the Prkdc and Il2rg genes (referred to as F344-scid gamma [FSG] rats). SCID rats show several phenotypic differences from SCID mice, including growth retardation, premature senescence, and a more severe immunodeficiency without "leaky" phenotypes. Double-knockout FSG rats show an even more immunocompromised phenotype, such as the abolishment of natural killer cells.Finally, xenotransplantation of human induced pluripotent stem cells, ovarian cancer cells, and hepatocytes shows that SCID and FSG rats can act as hosts for xenogeneic tissue grafts and stem cell transplantation and may be useful for preclinical testing of new drugs., 重症免疫不全SCIDラットの作製 : ヒトiPS細胞、がん細胞、肝細胞をラット体内で培養することに成功. 京都大学プレスリリース. 2012-09-14.
- Published
- 2012
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