NRG Mouse Model Development Services

In the rapidly evolving field of radionuclide drug conjugate (RDC) development, the radiation-resistant NRG mouse model emerges as a pivotal preclinical tool for advancing targeted radiopharmaceutical development. Offering a robust platform for evaluating RDC efficacy, safety, and biodistribution, Alfa Cytology's specialized NRG mouse development services are tailored to support pharmaceutical companies and researchers in accelerating their RDC development pipelines.

Overview of NRG Mouse Model

The NRG mouse model is crucial for humanized mouse model research, as it provides a significantly immunodeficient platform. The NRG mouse carries two mutations on the NOD genetic background, a targeted knockout of the recombination activation gene-2 (Rag2) and a knockout allele of the interleukin-2 receptor (IL-2R) common gamma chain (IL2rγ). The immunodeficiency caused by Rag2 mutations results in the absence of functional B and T lymphocytes. The knockout of IL2rg prevents cytokine signaling, thus resulting in the absence of functional NK cells.

Fig.1 Convection-enhanced delivery of ¹⁷⁷Lu-labeled gold nanoparticles treats orthotopic GBM in NRG mice. (Georgiou, C. J., et al., 2023)

This severe immunodeficiency allows the mice to be humanized through the engraftment of human CD34⁺ hematopoietic stem cells (HSC) and patient-derived xenografts (PDX). NRG mice also tolerate significantly higher doses of irradiation conditioning and genotoxic drugs than mice engineered with a scid mutation in the DNA repair enzyme Prkdc (NSG).

Applications of the NRG Mouse Model

Widely utilized in oncology and radiopharmaceutical research, this model enables precise assessment of radiopharmaceutical targeting, dosimetry, and therapeutic index. Applications include evaluating tumor-specific uptake of radionuclides, monitoring therapy response via imaging techniques such as SPECT/CT, and investigating off-target effects in biodistribution studies.

Advantages of the NRG Mouse Model

The NRG mouse model offers a superior immunodeficient platform characterized by enhanced radiation resistance and an immunocompromised state with high xenograft compatibility. This combination overcomes critical limitations of previous models, enabling more robust and reliable humanized model generation.

Our Services

Providing end-to-end NRG mouse model development, Alfa Cytology's services encompass custom model generation, validation, and comprehensive study design for RDC efficacy and safety profiling. From initial consultation to data analysis, we offer tailored solutions, including animal model establishment, in vivo imaging, and histopathological evaluations, all backed by rigorous quality control and regulatory compliance.

Strain Details for NRG Mouse

Case Study: NRG Mouse Model Development

A study was conducted by us to analyze the survival rates of NPG and NRG mice under varying doses of X-ray irradiation. Data indicated that the lethal radiation dose for NRG mice was 2-3 times higher than that for NPG mice, underscoring the stronger radio-tolerance of the NRG strain. This robust radio-tolerance was critical for preclinical studies involving high-dose radiation conditioning, particularly in the context of radiopharmaceutical development.

Fig.2 Survival analysis of NPG and NRG mice post X-ray irradiation. (A) Survival curve of NPG mice following irradiation. (B) Survival curve of NRG mice following irradiation.

Further validating its utility in oncology research, the NRG model supported robust engraftment and growth of human-derived tumor xenografts. Studies using the A549 human non-small cell lung cancer cell line confirmed that tumor growth in NRG mice was comparable to that observed in the well-characterized NPG model, ensuring reliable and reproducible humanized tumor model generation.

Fig.3 Engraftment and tumor growth of A549 xenografts in NRG and NPG Mice. Analysis of A549 tumor burden demonstrated equivalent tumorigenic potential and growth patterns in NRG mice compared to NPG controls.

In summary, our NRG mouse model represented a significant advancement over the NPG model, characterized by a dramatically increased tolerance to irradiation and a consequently higher resistance to mutagenic effects from radionuclides. The NRG mouse model achieved a severely immunocompromised state through the knockout of the Rag2 and IL2rg genes. This physiological characteristic enabled highly efficient human cell and tissue transplantation, establishing the NRG mouse as an ideal platform for generating humanized tumor models. These attributes were specifically advantageous for the evaluation of targeted therapies, including radiopharmaceuticals and RDCs, providing a superior in vivo system for assessing their precise targeting capabilities and ultimate therapeutic efficacy.

Customized Solutions for RDC Development

Beyond providing the NRG mouse model, a comprehensive portfolio of specialized research services is available to support targeted radiopharmaceutical development. These include customized solutions for biodistribution imaging, precise dosimetry analysis, and systematic efficacy evaluation across humanized tumor models.

Leveraging deep expertise in radiolabeling and radiopharmaceuticals, Alfa Cytology delivers reliable, data-driven solutions to expedite your RDC research and development. For collaborative opportunities or to learn more about our NRG mouse model services, please contact us to explore how our platforms can address your specific project needs.

Reference

1. Georgiou, Constantine J et al. "Treatment of Orthotopic U251 Human Glioblastoma Multiforme Tumors in NRG Mice by Convection-Enhanced Delivery of Gold Nanoparticles Labeled with the β-Particle-Emitting Radionuclide, ¹⁷⁷Lu." Molecular Pharmaceutics 20.1 (2023): 582-592.

For research use only. Not intended for any clinical use.