1. Generation and Characterization of Severe Combined Immunodeficiency Rats
- Author
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Tomoji Mashimo, Akiko Takizawa, Junya Kobayashi, Yayoi Kunihiro, Kazuto Yoshimi, Saeko Ishida, Koji Tanabe, Ami Yanagi, Asato Tachibana, Jun Hirose, Jun-ichiro Yomoda, Shiho Morimoto, Takashi Kuramoto, Birger Voigt, Takeshi Watanabe, Hiroshi Hiai, Chise Tateno, Kenshi Komatsu, and Tadao Serikawa
- Subjects
Biology (General) ,QH301-705.5 - 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.
- Published
- 2012
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