B6RG Mouse
Product Name
B6RG Mouse
Product ID
C001367
Strain Name
C57BL/6JCya-Rag2em1Il2rgem1/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “B6RG Mouse (Catalog C001367) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Il2rg & Rag2
Gene Alias
gc, p64, [g]c, CD132, gamma(c), Rag-2
NCBI ID
Chromosome
Chr X (Mouse), Chr 2 (Mouse)
Datasheet
Strain Description
The IL2RG gene, also known as the CD132 gene, encodes the interleukin-2 receptor gamma chain (IL-2Rγ), an essential signaling component of many interleukin receptors, and a common receptor subunit for various key immune factors, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. These interleukin receptors are located on the surface of immune cells. When an interleukin binds to its receptor, it triggers a series of chemical reactions within the cell, promoting cell growth and division; thus, the IL-2 receptor gamma chain is also called the common gamma chain (γc). Mutations in IL2RG in humans can lead to X-linked severe combined immunodeficiency (X-SCID), characterized by a lack of T cells and natural killer cells and impaired B cell function, making patients highly susceptible to recurrent infections and typically not surviving past infancy [1-2]. In mice, knockout of the Il2rg gene results in severe deficiencies of B cells, T cells, and NK cells in bone marrow, peripheral blood, and spleen, displaying a severe immunodeficient phenotype [2].
The RAG2 gene encodes a protein that, together with the RAG1 protein, forms the RAG complex, playing 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) located adjacent to V, D, or J segments in the DNA. 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 occurs repeatedly in B and T cells, arranging the V, D, and J segments in various combinations. The resulting protein diversity provides a broader capability to recognize foreign invaders, allowing the body to combat infections effectively. RAG2 is essential in V(D)J recombination, not only catalyzing the reaction but also regulating it by controlling access to specific loci [3]. A lack of functional RAG2 protein can also lead to severe combined immunodeficiency (SCID). In mice, deleting the Rag2 gene results in the absence of V(D)J recombination, blocking the differentiation, development, and maturation of T and B cells, which lose their normal functions, leading to a SCID-like phenotype [4].
The B6RG mouse is a double gene knockout model of Rag2 and IL2rg on the C57BL/6 background. Homozygous B6RG mice develop normally and are fertile but do not produce mature T cells, B cells, or NK cells. They can be used in studies related to immune system deficiencies, cancer, toxicology, and xenotransplantation.
Reference
Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: from molecular mechanisms to human therapy. Nat Rev Immunol. 2018 Oct;18(10):648-659.
Cao X, Shores EW, Hu-Li J, Anver MR, Kelsall BL, Russell SM, Drago J, Noguchi M, Grinberg A, Bloom ET, et al. Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity. 1995 Mar;2(3):223-38.
Schatz DG. V(D)J recombination. Immunol Rev. 2004 Aug;200:5-11.
Hao Z, Rajewsky K. Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow. J Exp Med. 2001 Oct 15;194(8):1151-64.
Strain Strategy
Rag2 is located on chromosome 2 in mice, and exon 3 of the Rag2 gene was knocked out using gene editing technology. Il2rg is located on the X chromosome in mice, and exons 2-6 of the Il2rg gene were knocked out using gene editing technology. The two types of mice were then crossbred to obtain the B6RG double gene knockout mouse model.
Figure 1.Rag2 gene targeting program.
Figure 2. Il2rg gene targeting program.
Application Area
Research on immune system defects;
Research on cancer and xenotransplantation, etc.;
Toxicology research.
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