Nude mice are a specialized strain of laboratory rodents characterized by a distinct lack of body hair and a severely compromised immune system. This unique state results from a spontaneous genetic mutation, making them invaluable models in biomedical research since their discovery in the 1960s. Their inability to mount a typical immune response allows scientists to make significant strides in understanding disease progression and developing new therapeutic strategies.
The Genetic Basis for Immune Deficiency
The distinctive appearance and immune deficiency of the nude mouse stem from a recessive mutation in the Foxn1 gene (Forkhead box N1). This genetic flaw results in two observable characteristics: athrichia (lack of fur) and athymia (failure of the thymus gland to develop). The thymus is a lymphoepithelial organ whose primary function is the maturation of T-lymphocytes, commonly called T-cells.
Because the thymus is absent or deteriorated, T-cells cannot properly mature, leading to a largely non-functional adaptive immune system. T-cells are the primary orchestrators of cell-mediated immunity, responsible for directly killing infected or malignant cells and coordinating the overall immune response. Without these mature T-cells, the mice cannot execute complex immune functions, such as mounting a full defense against pathogens or rejecting foreign tissue.
Modeling Human Disease with Xenografts
The most significant application of the T-cell deficient nude mouse is its use in xenograft studies, which involves transplanting tissue from one species into another. A mouse with a normal immune system would use T-cells to immediately recognize and destroy foreign human tissue, a process known as graft rejection. The nude mouse bypasses this rejection mechanism because it lacks the T-cells necessary to initiate this specific adaptive response.
This unique biological permissiveness allows researchers to introduce human tumors, stem cells, or other human tissue into the mouse host. The human tissue can then successfully “engraft” or grow, retaining many of its original characteristics. This makes the nude mouse an indispensable tool for studying human cancers, allowing scientists to observe tumor growth, metastasis, and the effect of human-specific drug treatments in a whole-organism setting. The model is particularly useful for growing cell line xenografts, where cancer cells are injected directly into the mouse to form a tumor.
Scientific Constraints of the Nude Mouse Model
While the nude mouse is highly effective for many research applications, its immune deficiency is not absolute, presenting certain scientific constraints. The mutation specifically targets T-cell function, but other components of the immune system, such as B-cells and Natural Killer (NK) cells, remain functional. B-cells, which produce antibodies, are still present, though their function is impaired without T-cell help.
The presence of active NK cells can still cause the rejection of certain types of transplanted tissue, including some primary human tumors or hematopoietic cancer cells. Therefore, the nude mouse model is not universally suitable for all xenograft experiments, particularly those requiring complete suppression of the innate immune response.
Consequently, researchers often turn to more severely immunocompromised models, such as SCID or NOD-SCID mice, when a study requires the absence of NK cells and B-cells in addition to T-cells. These strains are necessary for studies demanding a near-total lack of immune activity.