RGD Reference Report - Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases. - Rat Genome Database

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Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases.

Authors: Mashimo, T  Takizawa, A  Voigt, B  Yoshimi, K  Hiai, H  Kuramoto, T  Serikawa, T 
Citation: Mashimo T, etal., PLoS One. 2010 Jan 25;5(1):e8870.
RGD ID: 2316325
Pubmed: PMID:20111598   (View Abstract at PubMed)
PMCID: PMC2810328   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0008870   (Journal Full-text)

BACKGROUND: Although the rat is extensively used as a laboratory model, the inability to utilize germ line-competent rat embryonic stem (ES) cells has been a major drawback for studies that aim to elucidate gene functions. Recently, zinc-finger nucleases (ZFNs) were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc. METHODOLOGY/PRINCIPAL FINDINGS: We report here on ZFN-induced gene targeting of the rat interleukin 2 receptor gamma (Il2rg) locus, where orthologous human and mouse mutations cause X-linked severe combined immune deficiency (X-SCID). Co-injection of mRNAs encoding custom-designed ZFNs into the pronucleus of fertilized oocytes yielded genetically modified offspring at rates greater than 20%, which possessed a wide variety of deletion/insertion mutations. ZFN-modified founders faithfully transmitted their genetic changes to the next generation along with the severe combined immune deficiency phenotype. CONCLUSIONS AND SIGNIFICANCE: The efficient and rapid generation of gene knockout rats shows that using ZFN technology is a new strategy for creating gene-targeted rat models of human diseases. In addition, the X-SCID rats that were established in this study will be valuable in vivo tools for evaluating drug treatment or gene therapy as well as model systems for examining the treatment of xenotransplanted malignancies.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Il2rg  (interleukin 2 receptor subunit gamma)
Il2rgem1Kyo  (interleukin 2 receptor subunit gamma; ZFN induced mutant 1, Kyo)
Il2rgem2Kyo  (interleukin 2 receptor subunit gamma; ZFN induced mutant 2, Kyo)

Genes (Mus musculus)
Il2rg  (interleukin 2 receptor, gamma chain)

Genes (Homo sapiens)
IL2RG  (interleukin 2 receptor subunit gamma)

Objects referenced in this article
Strain F344-Il2rgem1Iexas null Rattus norvegicus

Additional Information