title: Generation and characterization of severe combined immunodeficiency rats.
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.
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. tmashimo@anim.med.kyoto-u.ac.jp
authors.forename: Tomoji
authors.initials: T
authors.lastname: Mashimo
authors.forename: Akiko
authors.initials: A
authors.lastname: Takizawa
authors.forename: Junya
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kunihiro
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yoshimi
authors.forename: Saeko
authors.initials: S
authors.lastname: Ishida
authors.forename: Koji
authors.initials: K
authors.lastname: Tanabe
authors.forename: Ami
authors.initials: A
authors.lastname: Yanagi
authors.forename: Asato
authors.initials: A
authors.lastname: Tachibana
authors.forename: Jun
authors.initials: J
authors.lastname: Hirose
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Yomoda
authors.forename: Shiho
authors.initials: S
authors.lastname: Morimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Birger
authors.initials: B
authors.lastname: Voigt
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiai
authors.forename: Chise
authors.initials: C
authors.lastname: Tateno
authors.forename: Kenshi
authors.initials: K
authors.lastname: Komatsu
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
mesh_terms: D000818:Animals; D051747:DNA-Activated Protein Kinase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation; D051381:Rats; D011922:Rats, Mutant Strains; D016511:Severe Combined Immunodeficiency; D014183:Transplantation, Heterologous
chemical_list: D053631:Interleukin Receptor Common gamma Subunit; D051747:DNA-Activated Protein Kinase