Immunobiology of congenitally athymic-asplenic mice

Congenitally athymic-asplenic mice on an outbred N:NIH(S) background were produced by the mating of nude by hereditarily asplenic (Dh/+)mice. Athymic-asplenic mice survive for up to 9 months, under specific pathogen free conditions, with no evidence for increased risk of spontaneous neoplasia. Although lymphocyte surface markers and sera immunoglobulin levels of athymic-asplenic mice are similar to their nude and asplenic littermates, there are a number of significant differences. In particular, levels of sera IgA are higher than nude, but lower than either nu/+ or Dh/+ mice, related perhaps to the increased histiocytic engorgement of Peyer's patches. Athymic-asplenic mice have normal haematocrit, haemoglobin, and reticulocyte counts, but are markedly leucopenic, have a thrombocytosis and an increased number of bone marrow CFU-C. As expected, the response of the athymic-asplenic mice to the T cell mitogen PHA is markedly reduced. However, levels of Thy 1.2 bearing cells, while reduced compared to either nu/+ or Dh/+ littermates, are significantly higher than nude mice in both Peyer's patches and lymph nodes. Further, they, like their nude littermates, fail to respond to sheep red blood cell immunization. Nonetheless, athymic-asplenic mice appear more immunologically compromised than nude mice. Indeed, there is an elevated rate of growth and a lower inoculated cell threshold needed for successful transplantation of a human malignant melanoma. Finally, there was no evidence for auto-antibody production in mice up to 9 months of age. Congenitally athymic-asplenic mice can be used for a variety of studies in which other immunologically deprived mouse mutants are desired.