Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice
Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice
复制标题
DOI：
10.1038/90795
复制
发表时间：
2001-08-01
影响因子：
46.9
通讯作者：
Kohno, K
中科院分区：
文献类型：
--
作者：
Saito, M;Iwawaki, T;Kohno, K
特异性细胞消融是分析细胞在体内功能的一种有效方法。我们已经开发了一种简单而敏感的方法，用于转基因小鼠的条件细胞消融，称为“毒素受体介导的细胞敲除”。我们使用肝细胞特异性启动子在转基因小鼠中表达白喉毒素（DT）受体，发现注射DT可引起暴发性肝炎。三个独立建立的转基因细胞系表明，肝细胞对DT的敏感性与DT受体的表达水平之间存在良好的相关性。此外，在大剂量的DT注射范围内，肝细胞损伤程度易于控制，其他细胞或组织未见明显异常。该系统可用于生成疾病小鼠模型，并用于研究细胞损伤或丢失后组织的恢复或再生。由于DT在生长细胞和非生长细胞中都是一种有效的蛋白质合成抑制剂，因此该方法适用于小鼠或其他DT不敏感动物的广泛细胞和组织。
Specific cell ablation is a useful method for analyzing the in vivo function of cells. We have developed a simple and sensitive method for conditional cell ablation in transgenic mice, called "toxin receptor-mediated cell knockout." We expressed the diphtheria toxin (DT) receptor in transgenic mice using a hepatocyte-specific promoter and found that injection of DT caused fulminant hepatitis. Three independently established transgenic lines demonstrated a good correlation between the sensitivity of hepatocytes to DT and the expression level of the DT receptors. Moreover, the degree of hepatocyte damage was easily controlled over a wide range of doses of injected DT without any obvious abnormalities in other cells or tissues. This system is useful for generating mouse models of disease and for studying the recovery or regeneration of tissues from cell damage or loss. As DT is a potent inhibitor of protein synthesis in both growing and non-growing cells, the method is applicable to a wide range of cells and tissues in mice or in other DT-insensitive animals.