B6RG Mouse

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.