BRG Mouse

The IL2RG gene encodes the interleukin-2 receptor gamma chain (IL-2Rγ), also known as the common gamma chain (γc). This receptor subunit is shared by several immune factors, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. When these cytokines bind to their receptors, they promote cell growth and division. Mutations in the IL2RG gene can lead to X-linked severe combined immunodeficiency (X-SCID), a condition characterized by a lack of T cells and natural killer cells, and non-functional B cells. As a result, patients with X-SCID are highly susceptible to recurrent infections and are unable to survive beyond infancy ^[1-2]. In mice, knockout of the Il2rg gene leads to severe depletion of B cells, T cells, and NK cells ^[2].

The RAG2 gene encodes a protein that forms the RAG complex with the RAG1 protein. This complex plays a crucial role in V(D)J recombination during B and T cell maturation. The RAG complex attaches to a section of DNA called a recombination signal sequence (RSS), next to a V, D, or J segment, and makes small cuts in the DNA so that the segment can be separated and moved. This process is repeated multiple times in different areas within B cells and T cells so that the V, D, and J segments are arranged in various combinations, providing greater recognition of foreign invaders ^[3]. A lack of functional RAG2 protein can lead to SCID. In mice, deletion of the Rag2 gene leads to loss of V(D)J recombination, resulting in blocked differentiation, development, and maturation of T cells and B cells ^[4].

BRG mice are models with the double knockout of Il2rg and Rag2 genes. This model presents more severe depletion of B cells, T cells, and NK cells as well as other severe combined immunodeficiency phenotypes than mice with knockout of either the Il2rg or Rag2 genes alone ^[5]. BRG mice can be used for research in various fields of oncology and immunology.