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huHSC-NKG-ProF Mouse
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huHSC-NKG-ProF Mouse
제품명
huHSC-NKG-ProF Mouse
제품 ID
C001543
품종 계통
huHSC-ProF-NOD.Cg-PrkdcscidIl2rgem1cya/Cya
Backgroud
NKG
상태
이 마우스 계통을 논문에서 사용할 경우, “huHSC-NKG-ProF Mouse (카탈로그 번호 C001543)은 Cyagen에서 구입하였습니다.”라고 명시해 주시기 바랍니다.
Immunodeficient Mice
Humanized Immune System Models
구매 가능한 제품 종류
연령
Genotype
성별
수량
표준 제공 조건은 최소 3마리의 이형접합(heterozygous) 보균자를 보장합니다. 동형접합(homozygous) 보균자 및/또는 특정 성별에 대한 브리딩 서비스도 제공됩니다.
가격 문의
Immunodeficient Mice
Humanized Immune System Models
기본 정보
검증 데이터
관련 자료
기본 정보
유전자명
유전자 별칭
gc, p64, [g]c, CD132, gamma(c)
NCBI ID
염색체
Chr X
MGI ID
--
Datasheet
품종 계통 설명
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 various immune cells. In addition, huHSC-NKG mice typically do not develop graft-versus-host disease (GvHD) and the reconstitution period can be long.
The huHSC-NKG-ProF mouse is the latest enhanced version of the huHSC-NKG series, where "Pro" indicates the enhanced series and "F" indicates full immune reconstitution. This mouse model uses advanced neonatal techniques optimised to develop a variety of human immune cells, including lymphoid T cells, B cells and NK cells, as well as myeloid dendritic cells (DCs), monocytes, macrophages and granulocytes. Due to its ability to reconstitute multiple types of human-derived immune cells, the huHSC-NKG-ProF mouse is also referred to as a fully humanised immune system mouse. It is an ideal model for immunological research, antibody-dependent cellular cytotoxicity (ADCC) studies and the development of tumor vaccines, cellular therapies and other biopharmaceuticals.
응용 분야
Tumor Immunology Research: Development of drugs such as immune checkpoint inhibitors, tumor vaccines, allogeneic cell therapies, and oncolytic viruses, as well as investigations into mechanisms that reverse T cell exhaustion, antibody-dependent cellular cytotoxicity (ADCC), and tumor-specific immunity；
Autoimmune Disease Research: Evaluation of the mechanisms underlying the onset of autoimmune diseases and the exploration of therapeutic strategies；
Drug Metabolism and Toxicity Research: Assessment of candidate compounds' pharmacokinetic properties and toxic effects in vivo.
검증 데이터
1. Survival and Growth Curves
Figure 1. Survival and body weight changes in NKG mice following human hematopoietic stem cells (HSCs) transplantation.
2. Reconstitution of Human Leukocytes in Peripheral Blood
Human cord blood-derived HSCs were transplanted into NKG mice for human immune system reconstitution. Once the reconstitution stabilized, the proportion of human CD45+ leukocytes reached approximately 40%-60%.
Figure 2. Reconstitution of human CD45+ leukocytes in the peripheral blood of NKG mice following transplantation of human HSCs.
3. Reconstitution of Human T Cells and B Cells in Peripheral Blood
T cell reconstitution began by week 10 post-transplantation, with average T cell levels reaching 50% by week 14. The average proportion of B cells was approximately 10%-20%.
Figure 3. Reconstitution of human T cells and B cells in the peripheral blood of NKG mice following transplantation of human HSCs*.
*Based on our internal testing, there may be variations in T cell reconstitution times depending on the HSC donor. Following process optimization, T cells can generally be reconstituted by week 10 and stabilized by week 14 after the transplantation of most HSC donors.
*Based on our internal testing, there may be variations in T cell reconstitution times depending on the HSC donor. Following process optimization, T cells can generally be reconstituted by week 10 and stabilized by week 14 after the transplantation of most HSC donors.
4. Reconstitution of Human NK Cells and Monocytes in Peripheral Blood
The average reconstitution proportion of NK cells remained between 20%-40%, while monocyte reconstitution in peripheral blood was observed at 1%-3%, with a higher proportion in the spleen (see spleen data section).
Figure 4. Reconstitution of human NK cells and monocytes in the peripheral blood of NKG mice following transplantation of human HSCs.
5. Proportion and Subtypes of Humanized Immune Cells in the Spleen After 14 Weeks of Reconstitution
Spleen tissues were collected 14 weeks after transplantation of human cord blood-derived HSCs into NKG mice, and the proportion and subtypes of humanized immune cells were analyzed. Results indicated that the average proportion of humanized immune cells reached 50%, with T cells comprising 40%-50% of the total human immune cells, B cells approximately 20% (higher than that in peripheral blood), NK cells around 20%, and total myeloid cells making up 20%-25% (also higher than in peripheral blood).
Figure 5. Proportion and subtypes of humanized immune cells in the spleen.
6. Subtype Analysis of Myeloid Cells in the Spleen After 14 Weeks of Reconstitution
Spleen tissues were collected 14 weeks after transplantation of human cord blood-derived HSCs into NKG mice for myeloid cell subtype analysis. Results showed that various myeloid subtypes were reconstituted, including granulocytes, different types of monocytes (Classical, Intermediate, Nonclassical), and macrophages (M1-macrophage, M2-macrophage). In the absence of tumors, M1-macrophages were more prevalent, but polarization towards M2-macrophages may occur with tumor progression. Classical dendritic cells (cDC) constituted 7% of total myeloid cells, providing a foundation for antigen processing and presentation.
Figure 6. Subtype analysis of myeloid cells in the spleen.
7. Application Cases
（1）mRNA Tumor Vaccine Treatment for Melanoma A375
Following treatment with the mRNA tumor vaccine, the tumor suppression rate for melanoma A375 reached 38.75%. In antigen-specific T cell assays, the vaccine treatment group exhibited significantly increased proportions of tetramer and IFN-γ, indicating the presence of functional human T cells and dendritic cells in the huHSC-NKG-ProF mice model, which may serve as an effective tool for preclinical tumor vaccine efficacy studies.
Figure 7. A case study using huHSC-NKG-ProF mice for mRNA tumor vaccine development.
（2）Rituximab Treatment for Burkitt’s Lymphoma Raji
Following four treatments with Rituximab, the tumor suppression rate reached 77%, demonstrating significant efficacy and indicating the presence of functional human NK cells in the huHSC-NKG-ProF mice.
Figure 8. A case study using huHSC-NKG-ProF mice for antibody drug development.
（3）Autoimmune Disease-Colitis Model
In this experiment, C57BL/6 and huHSC-NKG-ProF mice were fed 3% DSS. After 7 days, similar colitis phenotypes, including ulcers, intestinal mucosal damage, tissue edema and congestion, and glandular structure disruption, were observed in both huHSC-NKG-ProF and C57BL/6 mice, indicating that huHSC-NKG-ProF mice can be utilized to construct humanized colitis models.
Figure 9a. A case study using huHSC-NKG-ProF mice to establish a humanized colitis model.
Figure 9b. A case study using huHSC-NKG-ProF mice to establish a humanized colitis model.
관련 자료
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