Transgenic mice expressing the diphtheria toxin receptor are sensitive to the toxin

Whereas diphtheria and the mechanism of action of diphtheria toxin, the bacterial molecule that induces the disease, have been studied and understood for some time, the receptor that allows animal cells to bind the toxin escaped identification until recently. The receptor was identified by its ability to confer toxin‐sensitivity to mouse cells, which are normally toxin‐resistant. Although mice are also naturally resistant, we now demonstrate that transgenic mice expressing the diphtheria toxin receptor are as sensitive to the toxin as are humans and other toxin‐sensitive animals. These transgenic mice provide a suitable model for studying modern antidotes for diphtheria.

[1]  Jeong-Heon Cha,et al.  Receptor-Based Antidote for Diphtheria , 2002, Infection and Immunity.

[2]  J. Richardson,et al.  Microsomal triglyceride transfer protein expression during mouse development. , 2000, Journal of lipid research.

[3]  Kathryn N. Ivey,et al.  Cell Surface Monkey CD9 Antigen Is a Coreceptor That Increases Diphtheria Toxin Sensitivity and Diphtheria Toxin Receptor Affinity* , 2000, The Journal of Biological Chemistry.

[4]  Ubiquitous postnatal LoxP recombination using a doxycycline auto‐inducible Cre transgene (DAI‐Cre) , 2000, Genesis.

[5]  Wen-Hwa Lee,et al.  Temporal, spatial, and cell type–specific control of Cre-mediated DNA recombination in transgenic mice , 1999, Nature Biotechnology.

[6]  L. Eidels,et al.  Toxin binding site of the diphtheria toxin receptor: loss and gain of diphtheria toxin binding of monkey and mouse heparin‐binding, epidermal growth factor‐like growth factor precursors by reciprocal site‐directed mutagenesis , 1998, Molecular microbiology.

[7]  J. Miyazaki,et al.  A transgenic mouse line that retains Cre recombinase activity in mature oocytes irrespective of the cre transgene transmission. , 1997, Biochemical and biophysical research communications.

[8]  D. Russell,et al.  Expression cloning of a diphtheria toxin receptor: Identity with a heparin-binding EGF-like growth factor precursor , 1992, Cell.

[9]  M. Klagsbrun,et al.  A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF , 1991, Science.

[10]  P. Leder,et al.  The cytomegalovirus enhancer: a pan-active control element in transgenic mice , 1990, Molecular and cellular biology.

[11]  W. Cieplak,et al.  Diphtheria toxin receptor. Identification of specific diphtheria toxin-binding proteins on the surface of Vero and BS-C-1 cells. , 1987, The Journal of biological chemistry.

[12]  Stephen H. Leppla,et al.  Receptor-mediated internalization and degradation of diphtheria toxin by monkey kidney cells. , 1979, The Journal of biological chemistry.

[13]  S. Leppla,et al.  Association of diphtheria toxin with Vero cells. Demonstration of a receptor. , 1978, The Journal of biological chemistry.

[14]  J. Middlebrook,et al.  Response of cultured mammalian cells to the exotoxins of Pseudomonas aeruginosa and Corynebacterium diphtheriae: differential cytotoxicity. , 1977, Canadian journal of microbiology.

[15]  A. M. Pappenheimer.  Diphtheria toxin. , 1952, Annual review of biochemistry.

[16]  R. Collier.  Diphtheria toxin: mode of action and structure , 1975, Bacteriological reviews.