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Generation and Characterization of Severe Combined Immunodeficiency Rats
- Source :
- Cell Reports, Vol 2, Iss 3, Pp 685-694 (2012)
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
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.<br />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.
- 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
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 2
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....4e3a6293bdb29ad6047dfb14df3dc7a8
- Full Text :
- https://doi.org/10.1016/j.celrep.2012.08.009