Practical development of genetically engineered animals as human disease models.
Since transgenic (Tg) mice were first produced in 1980, the technology to produce genetically engineered animals, such as Tg and knock-out mice, has advanced exponentially. These animals have contributed greatly to basic research at the molecular level and have proven to be powerful tools for elucidating complex biological processes. The effort that is required to develop and establish genetically engineered animals as models for human diseases or toxicologic studies is not always appreciated by researchers and laboratory animal scientists. Genetically engineered animals remain only candidates of defined animal models until they are developed for practical use, in accordance with their objectives, through cooperation between the researchers performing the experiments and laboratory animal scientists. The practical development of these animals consists of three steps: establishment as standardized laboratory animals through the setting of quality standards and the establishment of a production and supply system; establishment as defined animal models through confirmation of the usefulness and limitations of the animal in the purpose of use; and establishment of an in vivo experimentation system (an animal experimentation system), using the defined animal models. This report serves as an introduction to those that follow and describes our concept of how best to establish genetically engineered animals as valid animal models. The development of Tg mice carrying the poliovirus receptor gene (PVR) will be used as an example. The TgPVR mice were produced by the introduction of the human poliovirus receptor gene into the mouse genome, mainly to study the molecular mechanisms of pathogenesis of the virus. The value of these mice is that they mimic human and nonhuman primate susceptibility to poliovirus infection and thus serve as a model for the study of the disease and for the assessment of poliovirus vaccines. They are being touted as a replacement for nonhuman primates in the neurovirulence testing of oral poliovirus vaccine.
Nomura
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Central Institute for Experimental Animals, Kawasaki, Japan.
D000818:Animals; D004195:Disease Models, Animal; D005818:Genetic Engineering; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D011991:Receptors, Virus / Q000235:genetics
D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor