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Nat Biotechnol. 2002 Dec;20(12):1234-9. Epub 2002 Nov 18.

Conditional cell ablation by tight control of caspase-3 dimerization in transgenic mice.

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  • 1Department of Genetics, Development and Molecular Pathology, Cochin Institute, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.


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.

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