Abstract
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.
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Acknowledgements
We thank Y. Kaneda for plasmid p2335A-1, S. Shiosaka and S. Yoshida for in situ hybridization, Y. Tsunoda and Y. Kato for advice about transgenic techniques, S. Kawata and Y. Matsuzawa for histochemical analysis of transgenic mice and R. Ando for technical assistance. We also thank M. Lamphier and I. Farcasanu for critical reading of the manuscript.This work was supported by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan.
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Saito, M., Iwawaki, T., Taya, C. et al. Diphtheria toxin receptor–mediated conditional and targeted cell ablation in transgenic mice. Nat Biotechnol 19, 746–750 (2001). https://doi.org/10.1038/90795
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DOI: https://doi.org/10.1038/90795
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