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Generation and characterization of severe combined immunodeficiency rats.

Authors: Mashimo, T  Takizawa, A  Kobayashi, J  Kunihiro, Y  Yoshimi, K  Ishida, S  Tanabe, K  Yanagi, A  Tachibana, A  Hirose, J  Yomoda, J  Morimoto, S  Kuramoto, T  Voigt, B  Watanabe, T  Hiai, H  Tateno, C  Komatsu, K  Serikawa, T 
Citation: Mashimo T, etal., Cell Rep. 2012 Sep 27;2(3):685-94. doi: 10.1016/j.celrep.2012.08.009. Epub 2012 Sep 13.
Pubmed: (View Article at PubMed) PMID:22981234
DOI: Full-text: DOI:10.1016/j.celrep.2012.08.009

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.


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CRRD Object Information
CRRD ID: 8696027
Created: 2014-08-11
Species: All species
Last Modified: 2014-08-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.