NCG

Strain Name: NOD/ShiLtJGpt-Prkdcem26Cd52Il2rg em26Cd22 /Gpt

Strain Type: Knock-out

Strain ID: T001475

Background: NOD/ShiLtJGpt

Description

Severe immune-deficient strain NCG is established by GRISPR/Cas9 technology. Prkdc(Protein kinase, DNA activated, catalytic polypeptide)and Il2rg(Common gamma chain receptor)genes are knocked out on NOD/ShiltJGpt background. The genetic background of NOD/ShiltJNju makes this line have natural immunodeficiency, such as complement system and macrophage defects [1]. At the same time, the Sirpa on NOD/ShiltJNju has high affinity with human CD47, making it more suitable for colonization of human grafts (e.g. tumors and human cells) than other strains[2]. Loss of Prkdc gene leads to the inability of V(D)J recombination to occur, resulting in the inability of T cells and B cells to mature. Il2rg is a common subunit of various interleukin cytokine receptors, and the inactivation of Il2rg leads to the loss of six different cytokine signaling pathways[3], resulting in NK cell defects[4].Therefore, NCG is the most thorough mouse model of the immune-deficient to date, and is very suitable for Cell derived xenograft (CDX), Patient derived xenograft (PDX), human peripheral blood mononuclear cells (PBMC) and human hematopoietic stem cell(HSC) transplantation for immune reconstitution. The NCG has a long life cycle of 89 weeks, which is beneficial for long-term transplantation and pharmacodynamic evaluation. It’s also available in North American market.

Application

1. Humanized immune system reconstitution

2. Preclinical anti-tumor efficacy with CDX and PDX model

3. Immuno-oncology therapy

4. CAR-T therapy

5. Stem cell research

Next generation of NCG for human immune reconstitution

References

1. Shultz LD, Schweitzer PA, Christianson SW, et al. (1995). “Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice”. J. Immunol. 154 (1): 180‒91.

2. Takenaka K, Prasolava TK, Wang JC, et al. (2007). “Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells”. Nat. Immunol. 8 (12): 1313‒23.

3. Cao X, Shores EW, Hu-Li J, et al. (1995). “Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain”. Immunity. 2 (3): 223‒38.

4. Greiner DL, Hesselton RA, Shultz LD (1998). “SCID mouse models of human stem cell engraftment”. Stem Cells. 16 (3): 166‒177.

Data support

T/B/NK cell ratio assay

Proportion of CD3+ (T cell), CD19+(B cell), CD335+(NK cell) and IgM+ (mature B) cells is in the splenocytes from NOD/ShiLtJGpt, NOD-scid and NCG females was analyzed by flow cytometry after stained with appropriate antibody. The result indicate there was almost no detectable T cell, B cell and NK cell in NCG mouse, confirmed that NCG is the severe immune deficient model.