title: Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice.
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.
authors.affiliation: Research and Education Center for Genetic Information, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0101, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Iwawaki
authors.forename: C
authors.initials: C
authors.lastname: Taya
authors.forename: H
authors.initials: H
authors.lastname: Yonekawa
authors.forename: M
authors.initials: M
authors.lastname: Noda
authors.forename: Y
authors.initials: Y
authors.lastname: Inui
authors.forename: E
authors.initials: E
authors.lastname: Mekada
authors.forename: Y
authors.initials: Y
authors.lastname: Kimata
authors.forename: A
authors.initials: A
authors.lastname: Tsuru
authors.forename: K
authors.initials: K
authors.lastname: Kohno
mesh_terms: D000418:Albumins / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D004742:Enhancer Elements, Genetic; D066257:Heparin-binding EGF-like Growth Factor; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012038:Regeneration; D013997:Time Factors; D014018:Tissue Distribution; D000637:Transaminases / Q000097:blood; D014162:Transfection
chemical_list: D000418:Albumins; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D000637:Transaminases