General Information

Development

Using gene editing technology to obtain Rag2 gene knockout C57BL/6 mice, which are then crossed with NPG mice. In the offspring, individuals with Rag2 knockout, Il2rg knockout, NOD Sirpa, and non-homozygous scid genes are selected, and purebred NOD rag2 gamma (NRG) mice are obtained through interbreeding of heterozygous individuals. The Rag2 mutation results in the absence of T and B cells in the mice; Il2rg knockout leads to a decrease in the number of NK cells and loss of activity.

Compared with NPG mice, NRG mice also have deficiencies in T cells, B cells, NK cells, and macrophages, making them suitable as highly immunodeficient mice for establishing xenogeneic tissue and tumor transplantation models. However, because NRG mice lack the scid gene mutation, they are more resistant to radiation and better tolerate the efficacy of radiotherapy drug combinations. NRG mice can efficiently engraft human CD34⁺ hematopoietic stem cells (HSC) and patient-derived tumor xenografts (PDX), making them an ideal humanized base model mouse.

Phenotype

1. Absence of functional T, B, and NK cells in the peripheral blood of NRG mice

2. NRG survival curves at different irradiation doses

Fig1. Survival curves after irradiation in NRG mice

The results showed that NRG were more resistant to irradiation compared to NPG mice.

3. Tumorigenic curve of NRG (A549 cell line)

NRG Mice Applications

1. A xenograft tumor model.

2. GvHD model.

3. Tumor radiotherapy experimental research.

4. Research and development of new humanized animal models.

Reference

1. Pearson T, Shultz LD, Miller D, et al. Non-obese diabetic-recombination activating gene-1 (NOD-Rag1 null) interleukin (IL)-2 receptor common gamma chain (IL2r gamma null) null mice: a radioresistant model for human lymphohaematopoietic engraftment. Clin Exp Immunol. 2008, 154(2):270-284.

2. Brehm MA, Cuthbert A, Yang C, et al.  Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation. Clin Immunol. 2010, 135(1):84-98.

3. Maykel J, Liu JH, Li H, et al. NOD-scidIl2rg (tm1Wjl) and NOD-Rag1 (null) Il2rg (tm1Wjl) : a model for stromal cell-tumor cell interaction for human colon cancer. Dig Dis Sci. 2014, 59(6):1169-1179.