Lymphocyte deficient mice as hosts for xenograft of human cells

淋巴细胞缺陷小鼠作为人类细胞异种移植的宿主

• 批准号: 10559007
• 负责人: NAKAMURA Masataka
• 金额: $ 4.67万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10559007/
• 关键词: immunodeficiency; animal model; common γchain; RAG1・RAG2; knock-out mouse; human cancer; NK細胞

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.

自然和人为产生的突变小鼠在人类疾病研究中很有用。我们已经建立了缺乏γ链的基因靶向小鼠菌株，这是T和NK细胞开发所必需的。突变小鼠具有少量的T和B细胞，因此将小鼠与RAG-2基因缺陷小鼠交叉，以产生完全缺乏T，B和NK细胞的新菌株。 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 studioded xenograft transplantation of surgical specimens of human colorectal cancer (well or moderately differentiated adenocarcinoma) into subcutaneous pockets老鼠。淋巴细胞缺乏小鼠的7个标本在2至6个月中一直活着。在组织学上显示了肿瘤细胞入侵入血管或肌肉层。这些结果表明，严重免疫组合的小鼠为人类结直肠癌细胞的生活和生长提供了环境。

项目成果

Nagata,K.: "Selective expression of a novel G protein-coupled receptor by human T helper 2 cells." J.Immunol.162. 1278-1286 (1999)

Nagata,K.：“人类 T 辅助 2 细胞选择性表达新型 G 蛋白偶联受体。”

Nagata K.: "CRTH2, an orphan rceptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s)"FEBS Letters. 459. 195-199 (1999)

Nagata K.：“CRTH2 是 T 辅助细胞 2 细胞的孤儿受体，在嗜碱性粒细胞和嗜酸性粒细胞上表达，并对肥大细胞衍生因子做出反应”FEBS Letters。

Tanaka K.: "Differential production of prostaglandin D2 by human helper T call subsets"J. Immunol.. (In press). (2000)

Tanaka K.：“人类辅助 T 呼叫子集产生前列腺素 D2 的差异”J.

Iwanaga,Y.: "Human T-cell leukemia virus type I Tax protein has multiple distinct transforming activiteis in T-cells." J.Virol.73. 1271-1277 (1999)

Iwanaga,Y.：“人类 T 细胞白血病病毒 I 型 Tax 蛋白在 T 细胞中具有多种不同的转化活性。”

Tanaka, K.: "Differential production of prostaglandin D2 by human helper T cell subsets."J. Immunol.. (in press). (2000)

Tanaka, K.：“人类辅助 T 细胞亚群产生前列腺素 D2 的差异。”J.