NKG mice are a kind of severe immunodeficient mice generated by Cyagen by deleting the Il2rg gene from NOD-Scid genetic background mice. NKG mice exhibit deficiency of mature T cells, B cells, and functional NK cells, reduced complement activity, and weak phagocytosis of human-derived cells by macrophages, which are well suited for transplantation of human hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), adult stem cells and tissues, and patient-derived xenograft (PDX). NKG mice are currently recognized as one of the models with the highest degree of immunodeficiency. They are an excellent model that can be widely used for research in the fields of oncology, immunity, autoimmune diseases, immunotherapy, vaccines, graft-versus-host disease (GvHD), and drug safety evaluation.

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.

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.

The interleukin-2 receptor subunit gamma (IL2Rg or CD132) gene encodes a protein that is an important signaling component of many interleukin receptors and is a common receptor subunit for several important immune factors, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. IL2Rg is a glycoprotein expressed on the surface of most lymphocytes. In mammals, the IL2Rg gene is located on the X chromosome, and mutations in IL2Rg in humans can lead to X-linked severe combined immunodeficiency (X-SCID). B6-Il2rg KO mice were obtained by knocking out the expression of the Il2rg gene in C57BL/6JCya mice, which are severely deficient in B and T cells in peripheral blood and bone marrow and partially deficient in the spleen, while the mice show a severe immunodeficient phenotype with almost complete absence of NK cells in peripheral blood, spleen, and bone marrow. This strain can be used for research in the fields of oncology, immunology, infectious disease, and stem cell biology.

Etfa is located on chromosome 9 of mice. Nuclease Technology was used to design sgRNA; Etfa knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Erich6b is located on chromosome 14 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Erich6b conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.

Il2rg is located on chromosome X of mice. Nuclease Technology was used to design sgRNA; Il2rg knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Il2rg is located on chromosome X of mice. Nuclease Technology was used to design sgRNA; Il2rg knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Il2rg is located on chromosome X of mice. SgRNA and ssDNA were designed using Nuclease Technology; Il2rg conditional knockout mice were obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Il2rg is located on chromosome X of mice. Nuclease Technology will be used to design sgRNA; Il2rg knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.