Lymphocyte deficient mice as hosts for xenograft of human cells

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Naturally and artificially generated mutant mice are useful in human disease studies. We have established a gene targeted mouse strain lacking the γchain which is necessary for development of T and NK cells. The mutant mice have a small amount of T and B cells, thus the mice were crossed with RAG-2 gene deficient mice to generate a new strain completely lacking T, B and NK cells. Both mouse strains lacking γchain gene alone and γchain plus RAG-2 genes have been back-crossed to C57BL/6 and Balb/c over 8 generations.Using lymphocyte deficient C57BL/6 mice, we have studied xenograft transplantation of surgical specimens of human colorectal cancer (well or moderately differentiated adenocarcinoma) into subcutaneous pockets of the mice. Six speciman out of 7 have been alive in lympocyte defient mice as long as 2 to 6 months. Tumor cell invasion into a blood vessel or muscle layer was shown histologically. These results indicate that the severely immunocompomised mice provide environments for human colorectal cancer cells to live and grow invasively.