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Generation of severe combined immune deficiency (SCID) rats: Hosts for xenotransplantation of human stem cells and tissu

September 14th, 2012

A research group at Kyoto University Graduate School of Medicine, Institute of Laboratory Animals, has successfully generated severe combined immune deficiency (SCID) rats by using zinc-finger nuclease (ZFN) technology. SCID rats can serve as an important experimental model for pre-clinical drug testing, and be a valuable resource in various fields, such as stem cell research and translational research.

SCID mice are the most widely used animal model in immunology, biology, and clinical sciences, and as such, they have contributed enormously to our understanding of the mechanisms underlying immunodeficiency and DNA-repair, as well as being ideal hosts for allogeneic and xenogeneic tissue transplantation. Now, almost 30 years after the first SCID mice have been developed, we report the genetic engineering and the characterization of major immunological properties of the first SCID rats. Because rats are 10 times larger than mice, they are more suitable as model for physiological, pharmacological, toxicological, and transplantation studies and it is expected that they will be at least as popular in this field as SCID mice already are.

Interestingly, SCID rats showed several phenotypic differences compared with SCID mice, including growth retardation and a more severe immunodeficiency without any evidence of 'leaky' phenotypes. Furthermore, double knockouts for the Prkdc and Il2rg genes resulted in the generation of rats that were even more immunocompromized, referred to as FSG rats. We also showed that both SCID and FSG rats can serve as hosts for the xenotransplantation of human induced pluripotent stem (iPS) cells, ovarian tumor cells, and hepatocytes.

We believe that SCID and FSG rats will be an important experimental model that can be used for pre-clinical testing, drug development and to dissect specific properties of the immune system that are not accessible in the mouse or that are caused by different immunological properties like the MHC that is very variant from the mouse MHC. They will also be a valuable resource applicable to diverse fields, such as stem cell research and translational research. We believe that our findings will appeal to a broad readership due to the universal utilization of a rat model that is severely combined immune-deficient.

More information:
Generation and Characterization of Severe Combined Immune Deficiency Rats. Tomoji Mashimo et al. Cell Reports (Online publication, September 13, 2012. dx.doi.org/10.1016/j.celrep.2012.08.009

Provided by Kyoto University

Citation: Generation of severe combined immune deficiency (SCID) rats: Hosts for xenotransplantation of human stem cells and tissu (2012, September 14) retrieved 4 August 2026 from https://sciencex.com/wire-news/109070681/generation-of-severe-combined-immune-deficiency-scid-rats-hosts.html

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