Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice

Specific cell ablation is a useful method for analyzing the in vivo functio n of cells. We have developed a simple and sensitive method for conditional cell ablation in transgenic mice, called "toxin receptor-mediated cell kno ckout." 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 demon strated a good correlation between the sensitivity of hepatocytes to DT and the expression level of the DT receptors. Moreover, the degree of hepatocy te damage was easily controlled over a wide range of doses of injected DT w ithout 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 inh ibitor of protein synthesis in both growing and non-growing cells, the meth od is applicable to a wide range of cells and tissues in mice or in other D T-insensitive animals.