Nature Biotechnology
19, 746 - 750 (2001)
doi:10.1038/90795
Diphtheria toxin receptor−mediated conditional and targeted cell ablation in transgenic miceMichiko Saito1, 4, 5, Takao Iwawaki1, 5, Choji Taya2, Hiromichi Yonekawa2, Munehiro Noda1, Yoshiaki Inui1, Eisuke Mekada3, Yukio Kimata1, Akio Tsuru1
& Kenji Kohno11
Research and Education Center for Genetic Information, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0101. 2
Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613. 3
Division of Cell Biology, Institute of Life Science, Kurume University, Kurume, Fukuoka 839-0861, Japan. 4
Present address: Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. 5
These two authors contributed equally to this work.
Correspondence should be addressed to Kenji Kohno kkouno@bs.aist-nara.ac.jpSpecific 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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