Lymphocyte deficient mice as hosts for xenograft of human cells

自然和人工产生的突变小鼠可用于人类疾病研究。我们已经建立了一个基因靶向的小鼠品系，缺乏T和NK细胞发育所必需的γ链。突变小鼠具有少量的T和B细胞，因此将小鼠与RAG-2基因缺陷小鼠杂交以产生完全缺乏T、B和NK细胞的新品系。用γ链基因缺失和γ链基因缺失加RAG-2基因缺失的小鼠与C57 BL/6和Balb/c回交8代后，用淋巴细胞缺陷的C57 BL/6小鼠研究了人大肠癌（高、中分化腺癌）手术标本皮下移植。7只小鼠中有6只存活2 ~ 6个月。组织学上显示肿瘤细胞侵入血管或肌肉层。这些结果表明，严重免疫缺陷小鼠为人类结直肠癌细胞提供了生存和侵袭性生长的环境。

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.