• The recombinant-activating gene 2 (Rag2) plays an important role in the rearrangement and recombination of the genes of immunoglobulin and T cell receptor molecules during the initiation of V(D)J recombination. Loss of Rag2 protein leads to no mature T and B cells, the critical components of the adaptive immune system.
• Il2rg is known as the interleukin receptor common gamma chain, which is an important signaling component of many interleukin receptors, including IL2, IL4, IL7, IL9, IL15 and IL21. IL15 is the main cytokine promoting NK cell differentiation and maturation. Knockout of the Il2rg gene will result in no mature NK cells in mice.
• Double knockout of Rag2 and Il2rg genes in mice results in an absence of mature T/B/NK cells, thereby creating a severe immunodeficiency mouse model. It can be used to support research in many areas including immune system defections, virology research, inflammation research, cancer research, xenograft/transplant host etc.

The size and weight of thymus and spleen of B-CDG mice were significantly reduced compared to that of wild-type C57BL/6 mice. Thymuses and spleens were isolated from wild-type C57BL/6 mice and B-CDG mice (n=3, 7-week-old). A. Gross anatomy of thymuses; B. The size of spleen and thymus; C. Comparison of organ coefficients of spleen and thymus in wild-type C57BL/6 mice and B-CDG mice. Results showed that thymuses were not visualized in B-CDG mice. The size and weight of spleens in B-CDG mice were significantly reduced compared to that in wild-type C57BL/6 mice.  

Lymph nodes were not visualized in B-CDG mice dyed by Evans blue. Wild-type C57BL/6 mice and B-CDG mice (n=3) were sacrificed and intravenously injected with 10% Evens blue in the planta pedis. The red arrows indicate the lymph nodes in inguinal, axillary and mesenteric site of the mice. No lymph node was visualized in B-CDG mice.

Frequency of leukocyte subpopulations in bone marrow by flow cytometry. Bone marrow cells were isolated from male wild-type C57BL/6 mice and homozygous B-CDG mice (n=3, 6-week-old). A. Flow cytometry analysis of the bone marrow cells was performed to assess the frequency of leukocyte subpopulations. B. Frequency of T cell subpopulations. T cells, including CD4+ T cells, CD8+ T cells and Tregs, B cells and NK cells were not detectable in B-CDG mice. Frequency of neutrophils, monocytes and macrophages were increased in B-CDG mice compared to that in C57BL/6 mice, demonstrating that the development of T cells, B cells and NK cells in bone marrow were completely inhibited in B-CDG mice. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test.  *P < 0.05, **P < 0.01, ***p < 0.001.

Frequency of leukocyte subpopulations in spleen by flow cytometry. Splenocytes were isolated from male wild-type C57BL/6 mice and homozygous B-CDG mice (n=3, 6-week-old). A. Flow cytometry analysis of the splenocytes was performed to assess the frequency of leukocyte subpopulations. B. Frequency of T cell subpopulations. T cells, including CD4+ T cells, CD8+ T cells and Tregs, B cells and NK cells were not detectable in B-CDG mice. Frequency of dendritic cells, neutrophils, monocytes and macrophages were increased in B-CDG mice compared to that in C57BL/6 mice, demonstrating that the development of T cells, B cells and NK cells in spleen were completely inhibited in B-CDG mice. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test.  *P < 0.05, **P < 0.01, ***p < 0.001.

Frequency of leukocyte subpopulations in blood by flow cytometry. Blood cells were isolated from male wild-type C57BL/6 mice and homozygous B-CDG mice (n=3, 6-week-old). A. Flow cytometry analysis of the splenocytes was performed to assess the frequency of leukocyte subpopulations. B. Frequency of T cell subpopulations. T cells, including CD4+ T cells, CD8+ T cells and Tregs, B cells and NK cells were not detectable in B-CDG mice. Frequency of dendritic cells, neutrophils and macrophages were increased in B-CDG mice compared to that in C57BL/6 mice, demonstrating that the development of T cells, B cells and NK cells in blood were completely inhibited in B-CDG mice. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test.  *P < 0.05, **P < 0.01, ***p < 0.001.