NODSCID

NOD/SCID mice are a widely used immunodeficient strain produced by crossing Non-Obese Diabetic (NOD) mice with a severe combined immunodeficiency mutation (SCID, Prkdcscid). The resulting animals are severely compromised in adaptive immunity, making them particularly suitable for studies that require engraftment of foreign cells or tissues.

The genetic basis of the strain is a Prkdcscid mutation on an NOD genetic background. This mutation disrupts V(D)J recombination, preventing the development of functional T and B lymphocytes. NK cell activity is markedly reduced, and lymphoid organs are underdeveloped. As a consequence, NOD/SCID mice lack humoral and cellular immune responses, allowing successful engraftment of human cells and tissues in many experimental settings. Some residual innate immune functions remain, and over time a phenomenon known as leaky SCID can lead to detectable, low-level lymphocytes.

Applications of NOD/SCID mice center on xenograft and humanization experiments. They are frequently used to grow human tumor xenografts, transplant human hematopoietic stem cells to generate humanized immune systems, and study infectious diseases in a human cell–bearing environment. The model supports long-term engraftment of various human cell types, enabling preclinical research in oncology, immunology, and virology.

Limitations include partial residual immunity, risks of infections, and the need for strict pathogen-free housing and handling. Their short lifespan in some conditions and the possibility of adoptive immune cell reconstitution can complicate long-term studies. Related strains, such as NSG (NOD/SCID gamma chain knockout), offer further immunodeficiency by eliminating the IL-2 receptor gamma chain, increasing engraftment efficiency for certain human tissues.