NKG-hIL6 Mice

Catalog Number: I001176

Genetic Background: NKG

Strain Description

NKG mice are a type of severe immunodeficient mouse developed by Cyagen by deleting the Il2rg gene from the NOD-Scid strain. This strain lacks mature T, B, and NK cells, exhibits reduced complement activity, and weak macrophage phagocytosis of human cells. As a result, NKG mice can efficiently engraft human hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), patient-derived xenografts (PDX), or adult stem cells and tissues.

In immunology research, direct studies on mice may not fully represent the human immune system due to physiological and immune system differences. However, by transplanting human peripheral blood mononuclear cells (PBMCs) or hematopoietic stem cells (HSCs) into immunodeficient mice, we can partially or completely replace the mouse immune system with a human counterpart. This approach enables in vivo simulation of human immune system function, providing an effective model for studying human immunity. In practical human-mouse xenotransplantation, using standard immunodeficient mice for transplantation may lead to differences in transplant efficiency due to the absence of specific human growth factors and supportive stromal cells within the mouse. Genetically modifying immunodeficient mice through gene editing techniques is a common strategy to enhance xenotransplantation efficiency.

Interleukin-6 (IL-6) is a cytokine that plays a crucial role in inflammation and B cell maturation. It is primarily produced and secreted into the bloodstream at acute and chronic inflammatory sites. IL-6 induces transcriptional inflammatory responses through its receptor, IL6Rα. Research indicates that immunodeficient mice carrying the human IL6 gene effectively enhance the differentiation of human monocytes and macrophages during HSC reconstruction ^[1]. NKG-hIL6 mice were constructed by introducing the human IL6 gene into the genome of NKG mice. Compared to NKG mice, NKG-hIL6 mice can efficiently and rapidly rebuild human CD45+ leukocytes during HSC reconstruction. These mice are valuable for developing tumor immunotherapies and drug evaluations.

Strain Strategy

The human IL6 gene was integrated into the genome of NKG mice using gene editing techniques.

Application

• Construction of an immune system humanized mouse model;
• Research on the human immune system and hematopoietic systems;
• Human-derived cell line xenograft (CDX) and patient-derived xenograft (PDX).
  
  

Validation Data

1. Expression of human IL6 protein

Figure 1. Human IL6 protein expression in the serum of NKG-hIL6 mice and wild-type (WT) mice. Mouse serum was collected and subjected to ELISA detection. The results demonstrate that both homozygous (Homo) and heterozygous (Hemi) NKG-hIL6 mice express human IL6 protein.

2. huCD34+ HSC immune reconstitution

Figure 2. Proportions of human CD45+ leukocytes, T cells, and B cells in the peripheral blood of NKG-hIL6 mice after human HSC transplantation. Four-week-old female NKG-hIL6 mice and NKG mice were selected, and human CD34+ HSCs were transplanted via tail vein injection. The results demonstrate that NKG-hIL6 mice rapidly reconstitute human CD45+ leukocytes. Compared to NKG mice, they exhibit significantly improved reconstitution efficiency and levels. Additionally, the reconstitution effects of T and B cells in NKG-hIL6 mice are comparable to those in NKG mice, while NK cells do not show effective reconstitution (data not shown).

References

[1] Hanazawa A, Ito R, Katano I, Kawai K, Goto M, Suemizu H, Kawakami Y, Ito M, Takahashi T. Generation of Human Immunosuppressive Myeloid Cell Populations in Human Interleukin-6 Transgenic NOG Mice. Front Immunol. 2018 Feb 2;9:152.