Rag2: A critical endonuclease initiating V(D)J recombination and immunity. 

• Gene Information: ocated on chromosome 11p12, the RAG2 gene encodes an essential component of the RAG multimer complex, working alongside RAG1 to catalyze V(D)J gene segment rearrangement. 
• Protein Expression: RAG2 expression is strictly restricted to developmentally immature B and T lymphocytes within the bone marrow and thymus, tightly regulated during specific stages of lymphopoiesis. 
• Signaling Pathway: The RAG1/2 complex recognizes recombination signal sequences, introducing double-strand DNA breaks that activate downstream non-homologous end-joining pathways to assemble functional antigen receptor genes. 
• Therapeutic Inhibition: While rarely inhibited directly, manipulating RAG2 pathways aids in studying primary immunodeficiencies like Omenn syndrome and developing gene-editing therapeutics to correct severe combined immunodeficiency.

Rag2

• The exon 3 that encode the entire protein (from ATG to stop codon) and 3’UTR region were knocked out in B-Rag2 KO mice, resulting in a disruption of the Rag2 gene.

Analysis of leukocyte subpopulations by flow cytometry in immune organs and blood. Splenocytes, peripheral blood, and thymocytes were isolated from C57BL/6 mice and homozygous B-Rag2 KO mice (female, 6-week-old, n = 3). Single live cells were gated on the CD45⁺ population and analyzed by flow cytometry as indicated. Values are expressed as mean ± SEM. Significance is determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001.

Analysis of T-cell subpopulations by flow cytometry in immune organs and blood. Splenocytes, peripheral blood, and thymocytes were isolated from C57BL/6 mice and homozygous B-Rag2 KO mice (female, 6-week-old, n = 3). Single live cells were gated on the TCRβ⁺ T-cell population and analyzed by flow cytometry as indicated. Values are expressed as mean ± SEM. Significance is determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001.

Q: What are the differences between B-Rag2 KO mice (110809) and B-CDG mice (112937)?

A: Both strains of mice are immunodeficient mice. B-Rag2 KO mice (110809) had the RAG2 gene knocked out, resulting in the absence of T and B cells. B-CDG mice (112937) had both the RAG2 and IL2RG genes knocked out, resulting in the absence of T, B, and NK cells, exhibiting a more severe immunodeficiency phenotype.