NSG Mice and Their Role in Advanced Biomedical Studies

NSG mice, or NOD scid gamma mice, are crucial in biomedical research due to their unique ability to host human cells, tissues, and tumors. This facilitates breakthroughs in oncology, immunology, and regenerative medicine by enabling precise studies of human diseases and therapies.

Underlying Genetic Modifications

These mice owe their research capabilities to specific genetic modifications: the NOD variant, scid mutation, and IL2rg deficiency. These collectively make them ideal for humanized model studies.

NOD Variant

The NOD (Non-Obese Diabetic) variant is a key genetic component of NSG mice. Originally developed to study Type 1 diabetes, the NOD strain has a mutation in the diabetes susceptibility locus, leading to immune deficiencies, including a lack of certain immune cells like NK cells. This immunodeficient background is essential for the engraftment of human cells, allowing researchers to explore human-specific diseases and therapies.

Scid Mutation

The scid (severe combined immunodeficiency) mutation is another critical alteration in NSG mice. Characterized by a defect in the DNA repair pathway, specifically the Prkdc gene, this mutation results in a lack of mature T and B cells, enhancing susceptibility to xenografts. This absence of adaptive immunity is invaluable for modeling human immune responses and diseases, providing a platform for studying human cancers and testing novel therapeutics.

IL2rg Deficiency

The IL2rg (interleukin 2 receptor gamma chain) deficiency amplifies the utility of NSG mice in research by leading to a lack of functional cytokine signaling pathways necessary for NK cell development. This results in profound immunodeficiency, facilitating the engraftment of human hematopoietic stem cells and the reconstitution of a human-like immune system. This deficiency is crucial for creating accurate humanized mouse models, supporting studies in oncology, infectious diseases, and immunotherapy.

Immunological Characteristics

The profound immunodeficient state of NSG mice is characterized by the absence of functional lymphocytes and NK cells, minimizing typical immune reactions like graft rejection. The NOD variant impacts macrophages and dendritic cells, while the scid mutation eliminates mature T and B cells. IL2rg deficiency disrupts cytokine signaling, further enhancing immunodeficiency. This combination facilitates the study of human cells and tissues, making NSG mice indispensable for human immunology research.

Studies have demonstrated NSG mice’s utility in modeling human immune conditions, such as autoimmune diseases and immunodeficiencies. For example, they have been used to model systemic lupus erythematosus and study HIV infection, providing insights into disease mechanisms and potential therapies.

Engraftment Features

The engraftment capabilities of NSG mice offer a versatile platform for studying human tissues and cells. Their profound immunodeficient state minimizes host-versus-graft reactions, allowing researchers to observe human cell behavior in a living organism.

NSG mice excel in supporting the engraftment of human hematopoietic stem cells, enabling detailed investigations into hematopoiesis and immune cell development. This aspect is particularly beneficial for research into blood disorders and immune system diseases.

Their ability to host human tumors provides a unique opportunity to study cancer biology and test therapeutic interventions. Patient-derived xenograft (PDX) models using NSG mice have been instrumental in understanding tumor heterogeneity and drug resistance mechanisms, facilitating the translation of laboratory findings into potential treatments.

Derived Variants

NSG mice have led to the creation of derived variants, each tailored to address specific research needs. These variants enhance certain features or introduce new capabilities, expanding the utility of the original NSG model.

One example is the NSG-SGM3 variant, which includes transgenes for human cytokines like IL3, GM-CSF, and SCF. This modification improves the engraftment of human immune cells, particularly those involved in myeloid lineage differentiation, making it useful for studying hematopoietic disorders and myeloid malignancies. These targeted enhancements allow for a more nuanced exploration of human cell interactions and disease progression, contributing to more effective therapeutic strategies.