A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration
A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration
复制标题
DOI：
10.1038/nmeth762
复制
发表时间：
2005-06-01
期刊：
影响因子：
48
通讯作者：
Waisman, A
中科院分区：
文献类型：
--
作者：
Buch, T;Heppner, FL;Waisman, A
一种用于谱系消除的新系统是基于白喉毒素受体（DTR）在小鼠细胞中的转基因表达和白喉毒素（DT）的应用。为了简化这种方法，我们产生了Cre诱导的DTR转基因小鼠（iDTR），其中Cre介导的STOP盒切除使细胞对DT敏感。我们通过分别与T细胞和B细胞特异性CD 4-Cre和CD 19-Cre菌株杂交来测试iDTR菌株，并观察到暴露于DT后T和B细胞的有效消融。在少突胶质细胞中表达Cre重组酶的MOGi-Cre/iDTR双转基因小鼠中，我们观察到腹膜内注射DT后的myetin投掷。因此，DT穿过血脑屏障并促进中枢神经系统中的细胞消融。值得注意的是，我们表明，发展DT特异性抗体反应是弱的，不中和，因此不妨碍DT的疗效。我们的研究结果验证了iDTR小鼠作为体内细胞消融工具的用途。
A new system for lineage ablation is based on transgenic expression of a diphtheria toxin receptor (DTR) in mouse cells and application of diphtheria toxin (DT). To streamline this approach, we generated Cre-inducible DTR transgenic mice (iDTR) in which Cre-mediated excision of a STOP cassette renders cells sensitive to DT. We tested the iDTR strain by crossing to the T cell- and B cell-specific CD4-Cre and CD19-Cre strains, respectively, and observed efficient ablation of T and B cells after exposure to DT. In MOGi-Cre/iDTR double transgenic mice expressing Cre recombinase in oligodendrocytes, we observed myetin toss after intraperitoneal DT injections. Thus, DT crosses the blood-brain barrier and promotes cell ablation in the central nervous system. Notably, we show that the developing DT-specific antibody response is weak and not neutralizing, and thus does not impede the efficacy of DT. Our results validate the use of iDTR mice as a tool for cell ablation in vivo.