Nude mice were first described in 1963 as hairless animals. The defect is the consequence of a recessive mutation of the "nu" gene, located on chromosome 11. It was subsequently found that these mice were also athymic, which rendered them highly susceptible to infectious diseases and necessitated that they be maintained in a strictly controlled microbiological environment. Because of the absence of a thymus, they are unable to mount T-cell-dependent immune responses and are especially lacking cell-mediated immunity. It is thus possible to transplant to these mice not only allogenic tissues, but also tissues of xenogenic origin.
T cells classically develop in the thymus, because the thymus provides the necessary epitheliostromal environment. In nude mice, there is no thymus, but T cells develop very slowly and may reach more than 10% of the amount found in normal mice. These T cells may express either the TCPab or the TCRgd T-cell receptors, although at a much lower density. The CD3 signaling module is also present, so the TCR is potentially functional.
B cells are present in normal amounts; but, as would be anticipated, isotypes that require T-cell help for class switching are absent or extremely reduced. Circulating IgM is present in normal amounts, but IgG1, IgG2a, IgG2b, and IgAare present only at very low levels. IgG3, which may be produced in response to T-independent immunogens, such as polysaccharides, is present in normal amounts. One role of the immune system that is frequently put forward is that of "immune surveillance"—that is, the elimination of potentially occurring tumors. In nude mice, however, there is apparently no impact on a possible increase in the emergence of spontaneous tumors, an observation probably explained by the presence of natural killer (NK) cells in increased numbers over normal mice. Because of the virtual absence of cell-mediated immunity, nude mice have been extensively used as recipients for tumor transplantation or for serial transfer of hybridomas as a source of monoclonal antibodies.
