RGD Reference Report - Generation and characterization of severe combined immunodeficiency rats. - Rat Genome Database

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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.
RGD ID: 8696027
Pubmed: PMID:22981234   (View Abstract at PubMed)
DOI: DOI:10.1016/j.celrep.2012.08.009   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PRKDCHumansevere combined immunodeficiency  ISORGD:1308982 RGD 
PrkdcRatsevere combined immunodeficiency  IMP  RGD 
PrkdcMousesevere combined immunodeficiency  ISORGD:1308982 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PrkdcRatdecreased body weight  IMP  RGD 
PrkdcRatdecreased immunoglobulin level  IMP  RGD 
PrkdcRatspleen hypoplasia  IMP  RGD 
PrkdcRatthymus hypoplasia  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Prkdc  (protein kinase, DNA-activated, catalytic subunit)

Genes (Mus musculus)
Prkdc  (protein kinase, DNA activated, catalytic polypeptide)

Genes (Homo sapiens)
PRKDC  (protein kinase, DNA-activated, catalytic subunit)

Objects referenced in this article
Strain F344-Prkdcem1Kyo null Rattus norvegicus
Strain F344-Prkdcem2KyoIl2rgem6Kyo null Rattus norvegicus
Gene Prkdcem1Kyo protein kinase, DNA activated, catalytic polypeptide; ZFN induced mutant1,Kyo Rattus norvegicus

Additional Information