SD-Rag2 KO Rats

Catalog Number: CR005

Strain Name: SD-Rag2em1/Cya

Genetic Background: Sprague-Dawley

Reproduction: Homozygote x Homozygote

 

Strain Description

The RAG2 gene encodes a protein that, together with the RAG1 protein, forms the RAG complex, which plays a crucial role in V(D)J recombination during the maturation of B and T cells. During V(D)J recombination, the RAG complex attaches to the recombination signal sequences (RSS) on the DNA, located next to the V, D, or J segments. The RAG complex cuts the DNA between the signal sequences and the segments, allowing the segments to separate and move to different regions of the genome. This process is repeated multiple times in B and T cells, resulting in various combinations of V, D, and J segments. The resulting protein diversity provides a broader range of recognition for foreign invaders, enabling the body to combat infections effectively. RAG2 not only participates in the catalytic reaction but also regulates the reaction by controlling access to specific loci [1].

The SD-Rag2 KO rat is an immunodeficient model with the Rag2 gene knocked out, and it can be used for extensive research in oncology and immunology. Studies have shown that the absence of functional RAG2 protein can lead to severe combined immunodeficiency (SCID). The deletion of the Rag2 gene in rats results in the absence of V(D)J recombination, blocking the differentiation, development, and maturation of T cells and B cells. This manifests as severe thymic hypoplasia, with no mature T and B cells, but a compensatory increase in NK cells [2-3]. In addition, Cyagen also offers the SDRG rat (Product Number: IR1023) with a double knockout of the Il2rg and Rag2 genes. Compared to the Rag2 gene knockout rats, the Il2rg and Rag2 double knockout rats exhibit a more severe phenotype of severe combined immunodeficiency.

Strain Strategy

Figure 1. Gene editing strategy of SD-Rag2 KO rat. The rat Rag2 gene is located on rat chromosome 3. Exon 3 of this gene is knocked out using gene editing technology.

Application

  • Oncology: Used for constructing CDX and PDX tumor models and screening and evaluating antitumor drugs.
  • Immunology: Research on the mechanisms of immune cell development and maturation, as well as the pathogenesis of immune diseases.
  • Pathogenic Microbiology: Research on the mechanisms of viral and bacterial infectious diseases.
  • Stem Cell Biology: Research on human stem cell transplantation.


Validation Data

1. T cells, B cells, and NK cells in peripheral blood


Figure 2. Comparison of Peripheral Blood T Cells, B Cells, and NK Cells in Female Wild-Type (WT) Rats and SD-Rag2 KO Rats. The composition of immune cells in the peripheral blood of WT and SD-Rag2 KO rats was analyzed by flow cytometry. The results show that, compared to WT rats, SD-Rag2 KO rats exhibit a deficiency of T and B cells in peripheral blood, with a significant increase in the proportion of NK cells.

 

2. T cells, B cells, and NK cells in the spleen


Figure 3. Comparison of Spleen T Cells, B Cells, and NK Cells in Female Wild-Type (WT) Rats and SD-Rag2 KO Rats. The composition of immune cells in the spleens of WT and SD-Rag2 KO rats was analyzed by flow cytometry. The results show that, compared to WT rats, SD-Rag2 KO rats exhibit a deficiency of T and B cells in the spleen, with a significant increase in the proportion of NK cells.

 

3. T cells, B cells, and NK cells in the thymus


Figure 4. Comparison of Thymus T Cells, B Cells, and NK Cells in Female Wild-Type (WT) Rats and SD-Rag2 KO Rats. The composition of immune cells in the thymus of WT and SD-Rag2 KO rats was analyzed by flow cytometry. The results show that, compared to WT rats, SD-Rag2 KO rats exhibit a deficiency of T and B cells in the thymus, with a significant increase in the proportion of NK cells.

 

References
[1]Schatz DG. V(D)J recombination. Immunol Rev. 2004 Aug;200:5-11.
[2]Noto FK, Adjan-Steffey V, Tong M, Ravichandran K, Zhang W, Arey A, McClain CB, Ostertag E, Mazhar S, Sangodkar J, DiFeo A, Crawford J, Narla G, Jamling TY. Sprague Dawley Rag2-Null Rats Created from Engineered Spermatogonial Stem Cells Are Immunodeficient and Permissive to Human Xenografts. Mol Cancer Ther. 2018 Nov;17(11):2481-2489.
[3]Liu Q, Fan C, Zhou S, Guo Y, Zuo Q, Ma J, Liu S, Wu X, Peng Z, Fan T, Guo C, Shen Y, Huang W, Li B, He Z, Wang Y. Bioluminescent imaging of vaccinia virus infection in immunocompetent and immunodeficient rats as a model for human smallpox. Sci Rep. 2015 Aug 3;5:11397.