1990-1991: Establishment of human poliovirus receptor transgenic mice
1991-1993: Establishment as a laboratory animal (standardization of characters and successful large-scale production) and development of methods for neurovirulence testing and safety assurance by castration (Levenbook and Nomura 1997)
1993-1995: World Health Organization (WHO) collaborative study of TgPVR21, 1st phase
1995-1997: WHO collaborative study of TgPVR21, 2nd phase
1997-1999: WHO collaborative study of TgPVR21, 3rd phase
1999: Approval of neurovirulence test of oral poliovirus vaccine alternative for monkeys by WHO Expert Committee on Biological Standardization
1988: Establishment of human proto-ras gene transgenic mouse
1990-1992: Backcrossing and establishment of congenics
1992-1996: Validation study for carcinogenicity testing in Japan (Yamamoto and others 1998)
1996-1999: Validation study for rapid carcinogenicity testing in the United States, the European Union, and Japan
As shown above, establishment of a novel laboratory animal from a genetically engineered animal is a lengthy process and requires many steps as follows: (1) establishing of a genetically engineered animal; (2) phenotyping and selection of candidate animals; (3) study of functions in purpose-oriented environments or experimentation (dramatyping); and (4) establishment of a human disease model as a laboratory animal.
Levenbook, I., and T. Nomura. 1997. Development of a neurovirulent testing system for oral poliovirus vaccine with transgenic mice. Lab. Anim. Sci. 47:118-120.
Yamamoto, S., K. Urano, H. Koizumi, S. Wakana, K. Hioki, K. Mitsumori, Y. Kurokawa, Y. Hayashi, and T. Nomura. 1998. Validation of transgenic mice carrying the human prototype c-Ha-ras gene as a bioassay model for rapid carcinogenicity testing. Environ. Health Perspect. 106(Suppl 1):57-69.