Conditional cell ablation by tight control of caspase-3 dimerization in transgenic mice
Conditional cell ablation by tight control of caspase-3 dimerization in transgenic mice
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DOI：
10.1038/nbt762
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发表时间：
2002-12-01
影响因子：
46.9
通讯作者：
Gilgenkrantz, H
中科院分区：
文献类型：
--
作者：
Mallet, VO;Mitchell, C;Gilgenkrantz, H
研究特定细胞类型丢失的影响是生物学中一种强有力的方法。在这里，我们提出了一种方法的基础上控制激活的凋亡机制。我们在转基因小鼠的肝脏中表达了一种含有二聚化（CID）结合位点的修饰的caspase-3化学诱导剂。在不存在CID的情况下，未检测到肝损伤，强调我们的系统中没有泄漏。相比之下，注射CID产生嵌合半胱天冬酶-3的活化，这导致剂量依赖性纯肝细胞消融，随后再生。该方法在生长和非生长细胞中均有效，因此适用于广泛的细胞和组织。此外，由于细胞凋亡已被描述在许多病理情况下，该系统是有用的，用于产生人类疾病的小鼠模型，以及用于研究细胞损失后的组织的恢复或再生。
Studying the effects of the loss of a specific cell type is a powerful approach in biology. Here we present a method based on the controlled activation of the apoptotic machinery. We expressed a modified caspase-3-containing chemical inducer of dimerization (CID)-binding sites in the livers of transgenic mice. In the absence of CID, no liver injury was detectable, underlining the absence of leakage in our system. In contrast, injection of the CID produced activation of the chimeric caspase-3, which led to a dose-dependent pure hepatocyte ablation with subsequent regeneration. This method is effective in both growing and nongrowing cells, and is therefore applicable to a wide range of cells and tissues. Moreover, because apoptosis has been described in numerous pathological circumstances, this system is useful for generating mouse models of human disorders as well as for studying the recovery or regeneration of tissues after cell loss.