huHSC-NKG Mice

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Catalog Number: C001328

Genetic Background: NOD-Scid


Strain Description

NKG mice (catalog number: C001316) are a kind of severe immunodeficient mice generated by Cyagen through deleting the Il2rg gene from NOD-Scid 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 the transplantation of human hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), adult stem cells and tissues, and patient-derived xenograft (PDX).

huHSC-NKG mice are immune system humanized mouse models constructed by transplanting human hematopoietic stem cells (HSC) into NKG mice after sub-lethal dose irradiation. This model has a long lifespan and can successfully reconstitute a variety of immune cells. Furthermore, huHSC-NKG mice typically do not develop graft-versus-host disease (GvHD) and the reconstitution period can be lengthy.

 

Female NKG mice aged 4-5 weeks were selected to inject CD34+ hematopoietic stem cells (HSCs) through the tail vein after irradiation, and the reconstitution period was 12-16 weeks.

Long-term research in the fields of tumor immunity, hematopoiesis, and gene therapy for hematologic and infectious diseases.

1. NKG mice (Adult) for human CD34+ HSC immune system reconstruction research

a. Survival curve

Figure 1. The survival curve of huHSC-NKG adult mice. The huHSC-NKG adult mice were free of graft-versus-host disease (GvHD) and maintained a high survival rate of over 70% after 150 days post-engraftment.

 

b. Growth curve

Figure 2. The growth curve of huHSC-NKG adult mice. The huHSC-NKG adult mice maintained normal weight gain after the transplantation of huHSC.

 

c. Proportion of human leukocytes

Figure 3. The proportion of human CD45+ cells in peripheral blood of huHSC-NKG adult mice. The percentage of human leukocytes gradually increased, and the average percentage of human CD45+ cells reached more than 60%.

 

d. Proportions of human T cells and B cells


Figure 4. Proportions of human T cells and B cells in huHSC-NKG adult mice. The reconstruction of the immune system in this model was dominated by B cells in the early stage. The proportion of B cells gradually decreased and the proportion of T cells gradually increased in the later stage. At 12 weeks post-engraftment, the proportion of T cells began to increase, reaching about 40% at week 16. The proportion of B cells was higher at the early stage, reaching 80%, and decreased to 15% at week 24.

 

e. Proportions of human NK cells and monocytes


Figure 5. Proportions of human NK cells and monocytes in huHSC-NKG adult mice. The proportions of NK cells and monocytes during immune system reconstitution were low. The average proportion of NK cells maintained at about 2% overall and the proportion of monocytes at week 16 was about 2%.

 

2. NKG mice (Newborn) for human CD34+ HSC immune system reconstruction research

a. Survival curve

Figure 6. The survival curve of huHSC-NKG newborn mice. The huHSC-NKG newborn mice were free of graft-versus-host disease (GvHD). The survival rate of huHSC-NKG newborn mice maintained more than 90% before 100 days post engraftment and the survival rate still maintained more than 80% nearly 150 days post engraftment, which was higher than that of the adult model.

 

b. Growth curve

Figure 7. The growth curve of huHSC-NKG newborn mice. The huHSC-NKG newborn mice maintained normal weight gain after the transplantation of huHSC.

 

c. Proportion of human leukocytes

Figure 8. The proportion of human CD45+ cells in peripheral blood of huHSC-NKG newborn mice. The percentage of human leukocytes gradually increased. The average percentage of human CD45+ leukocytes reached more than 40% after 8 weeks post engraftment and subsequently increased and maintained at about 60%.

 

d. Proportions of human T cells and B cells


Figure 9. Proportions of human T cells and B cells in huHSC-NKG newborn mice. Similar to the adult model, the reconstruction of the immune system in this model was dominated by B cells in the early stage. The proportion of B cells gradually decreased and the proportion of T cells gradually increased in the later stage. At 12 weeks post-engraftment, the proportion of T cells began to increase, reaching about 40% at week 14. The proportion of B cells was higher than 80% at the early stage and decreased continuously, dropping to 40% at week 20.

 

e. Proportions of human NK cells and monocytes


Figure 10. Proportions of human NK cells and monocytes in huHSC-NKG newborn mice. The proportions of NK cells and monocytes were higher in this newborn model than that in the adult model. The average percentage of NK cells was more than 10% in the early stage and maintained at about 5% in the later stage. The average percentage of monocytes was higher than 5%. Therefore, the newborn model is more suitable for studies related to myeloid cell targets.