Immunodeficient Mice

IMMUNODEFICIENT MICE

NCG

Strain Name: NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt
Strain Type: Knock Out
Strain Number: T0014755

STRAIN DESCRIPTION

NCG (NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt) ) mice are highly immunodeficient mice developed by knocking out two key genes, Prkdc and IL2RG, on the NOD/ShiLtJGpt background. This genetic combination results in the absence of functional T cells, B cells, and natural killer (NK) cells. The NOD background also contributes additional immune deficiencies, including defects in the complement system and macrophage function. Importantly, the presence of a human-compatible SIRPα protein enhances the engraftment of human cells and tumors. The deactivation of IL2RG further eliminates six cytokine signaling pathways, contributing to NK cell defects. Together, these features make NCG mice an ideal model for tumor studies such as CDX and PDX, as well as for human immune system reconstitution using PBMCs or CD34+ stem cells. With a long lifespan of over 89 weeks, NCG mice are well-suited for long-term transplantation and drug efficacy studies.

APPLICATIONS

Humanized immune system mouse models, e.g. humanized BLT mice, humanized PBMC mice and humanized CD34+ mice;

Human cell line-derived xenograft, patient-derived xenograft (CDX, PDX)

Efficacy evaluation (small molecular/macromolecular drugs, combination therapies);

Human cancer models

Stem-cell studies

VALIDATION DATA

1. NCG Peripheral Blood Immune Cell Sub-population Statistics

Peripheral blood of 7-week-old NOD, NOD-Scid and NCG mice was taken for flow assay to determine the ratio of their immune cell fractions. The results showed that compared with NOD, NOD-Scid had almost no T and B cells, the proportion of NK cells increased compensatorily, the proportion of DC cells, neutrophils, monocytes and eosinophils increased, and the proportion of macrophages decreased. Compared with NOD, NCG had almost no T, B, NK cells and macrophages, and the immunodeficiency was more complete than that of NOD-Scid.

Figure 1 NOD, NOD-Scid and NCG mice statistical plot of the percentage of peripheral blood immune cell fractions (n=5)

2. NCG Spleen Immune Cell Sub-population Statistics

The spleens of 7-week-old NOD, NOD-Scid and NCG mice were taken for flow assay to determine their immune cell fraction ratios. The results showed that compared with NOD, NOD-Scid had almost no T and B cells, the proportion of NK cells was compensatingly increased, and the proportions of DC cells, neutrophils, monocytes, eosinophils and macrophages were elevated. Compared with NOD, NCG had almost no T, B and NK cells and a higher degree of immunodeficiency.

Figure 2. NOD, NOD-Scid and NCG mice statistical plot of the percentage of splenic immune cell fractions(n=5)

3. NCG Growth Curve

Body weight analysis was performed for 16-week-old NCG mice. The results showed that the body weight of NCG male mice was generally higher than that of female mice.

Figure 3. Growth curve of NCG mice

4. NCG Tumorigenicity Test

Human breast cancer cell line BT-474, human colon cancer cell line COLO205, human pancreatic cancer cell line PANC1 and human ovarian cancer cell line SK-OV-3 were inoculated subcutaneously into 6-8 week old Nu/NOD-Scid/NCG mice at logarithmic growth stage, respectively, and the tumors grew in a gradient curve in size with time. (Tumor volume values are expressed as Mean±SEM).

Figure 4. NCG mice tumorigenicity test

PUBLICATIONS
  • Hu et al. (2022) – Interferon-α enhances anti-PD-1 therapy by altering glucose metabolism in liver cancer. Cancer Discovery. IF: 39.397
  • Ma et al. (2021) – pH-responsive HER2-targeted nanodrug for breast cancer using DNA tetrahedrons. Advanced Materials. IF: 30.849
  • Song et al. (2022) – Targeting METTL7B to reverse EGFR-TKI resistance in lung cancer. Molecular Cancer. IF: 41.444
  • Zhang et al. (2021) – Creatine promotes cancer metastasis via Smad2/3 activation. Cell Metabolism. IF: 22.4
  • Liu et al. (2022) – PRMT7 loss alters glycine metabolism to eliminate leukemia stem cells. Cell Metabolism. IF: 22.4
  • Zhang X-N et al. (2021) – Glioblastoma resistance to chemo enhanced by pericytes via CCL5-CCR5. Cell Research. IF: 25.617
  • Dai et al. (2022) – Bispecific CAR-T cells (CD5/CD7) reduce tumor antigen escape. Signal Transduction and Targeted Therapy. IF: 18.187
  • Dai et al. (2021) – m7G tRNA modification drives liver cancer progression. Molecular Cell. IF: 17.97
  • Hao et al. (2020) – Combining metabolic intervention with T cell therapy improves immunotherapy. Science Translational Medicine. IF: 17.956
  • Liu et al. (2021) – STAR receptors using TCR components show strong anti-tumor response. Science Translational Medicine. IF: 17.956
  • Yan et al. (2021) – NEAT1 suppresses AML stem cells by inhibiting Wnt signaling. Advanced Science. IF: 17.521
  • Luo et al. (2020) – ARID1A prevents squamous cell carcinoma and chemoresistance. Cell Death & Differentiation. IF: 12.067
  • Wu et al. (2022) – Cancer stem cell plasticity protects metastatic cells from ferroptosis. Nature Communications. IF: 14.919
  • Liu H et al. (2021) – Bispecific antibody (TROP2xCD3) inhibits triple-negative breast cancer. Journal for ImmunoTherapy of Cancer. IF: 12.469