Evaluation of three lines of immunodeficient mice for the study of spontaneous metastatic tumors

Various immunodeficient animals have been used as transplantation recipient s for studying the growth of human tumors. We have been assessing the value of immunodeficiencies for the study of naturally arising tumors, using a m odel system of transgenic mice that spontaneously develop cancer of the pan creas as a result of elastase promoter-driven expression of the large tumor antigen gene of simian virus 40. We previously reported the establishment of transgenic mice that carried the SCID and/or beige mutations, eliminatin g B- and T-cell function and reducing lytic NK cell activity, respectively. In SCID beige animals, metastasis rates and target organs for metastases w ere similar to those observed in humans with pancreatic cancer. We describe here analysis of subsequent more highly inbred generations of these mice. The data show that inbreeding has almost negated the value of these immunod eficiencies for enhancing disease progression, and we observe high rates of metastasis even in immunocompetent animals. The data suggest that SCID and beige immunodeficiencies may not always have the same value for the modeli ng of spontaneous tumors as they do for the study of xenografts.