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.

自然和人工产生的突变小鼠在人类疾病研究中很有用。我们已经建立了一个缺乏T和NK细胞发育所必需的γ链的基因靶向小鼠品系。突变小鼠有少量的T、B细胞，因此与RAG-2基因缺陷小鼠杂交，产生了一种完全缺乏T、B和NK细胞的新品系。两个单独缺失γ链基因和γ链加RAG-2基因的小鼠株系已经回交到C57BL/6和Balb/c，历经8代。我们利用淋巴细胞缺陷的C57BL/6小鼠，研究了人结直肠癌(高分化腺癌和中分化腺癌)手术标本的异种移植到小鼠皮下。在7个样本中，有6个样本在淋巴细胞违抗的小鼠体内存活了2到6个月。组织学显示肿瘤细胞侵入血管或肌肉层。这些结果表明，严重免疫合成的小鼠为人类结直肠癌细胞提供了侵袭性生长和生存的环境。

项目成果

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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.

Ohtani,K.: "Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T cell leukemia virus type I."J.Biol.Chem.. 273. 14119-14129 (1998)

Ohtani,K.：“由人 T 细胞白血病病毒 I 型癌蛋白 Tax 反式激活的 gp34 基因启动子调节的分子机制。”J.Biol.Chem.. 273. 14119-14129 (1998)

Ohtani, K., Tsujimoto, A., Tsukahara, T. Numata, N., Miura, S., Sugamura, K. & Nakamura, M.: "Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T-cell leukemia virus type I."J. Biol. Chem..

Ohtani, K.、Tsujimoto, A.、Tsukahara, T. Numata, N.、Miura, S.、Sugamura, K.