N:NIH(S)-nu/nu mice with combined immunodeficiency: a new model for human tumor heterotransplantation.

A new "nude" mouse model was developed by successive crossings and backcrossings between athymic nu/nu mice, on an N:NIH(S) background, and female CBA/N mice that have an X-linked immune defect in B-lymphocyte function. The resulting doubly congenic N:NIH(S(II-nu/nu mice maintained the marked thymic hypoplasia and poor development of hair of the nu/nu mice. In contrast to nu/nu and CBA/N mice, in this new mouse model both T-cell zones of lymph nodes and the spleen were depleted of lymphocytes. Lymphocytic follicles were rare and diminutive; not germinal centers were noted. The nodal cortical and paracortical areas were represented principally by connective tissue, endothelial cells, and macrophages, including giant multinucleated cells. No medullary cords were recognized. The mice with combined immunodeficiency supported the growth of human tumor xenografts and were susceptible to murine viral hepatitis.