BRG Mouse
Product Name
BRG Mouse
Product ID
C001436
Strain Name
BALB/cAnCya-Rag2em1Il2rgem1/Cya
Backgroud
BALB/cAnCya
When using this mouse strain in a publication, please cite “BRG Mouse (Catalog C001436) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Alias
Rag-2, gc, p64, [g]c, CD132, gamma(c)
Chromosome
Chr 2, Chr X
MGI ID
Datasheet
Strain Description
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.
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.
Song J, Willinger T, Rongvaux A, Eynon EE, Stevens S, Manz MG, Flavell RA, Galán JE. A mouse model for the human pathogen Salmonella typhi. Cell Host Microbe. 2010 Oct 21;8(4):369-76.
Strain Strategy
The Il2rg and Rag2 genes were knocked out in BALB/cAnCya mice to generate BRG mice. The targeting strategies for Il2rg and Rag2 knockout are presented below.
Figure 1. Targeting strategy for Rag2 knockout.
Figure 2. Targeting strategy for Il2rg knockout.
Application Area
<b>Oncology:</b> Investigating the mechanisms underlying tumor growth and metastasis, and evaluating the efficacy of antitumor drugs.
<b>Immunology:</b> Exploring the mechanisms of immune cell development and maturation, as well as the pathogenesis of immune diseases.
<b>Epidemiology:</b> Examining the mechanisms of viral and bacterial infectious disease pathogenesis.
<b>Stem Cell Biology:</b> Investigating the potential of human stem cell transplantation.
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