. "International Harmonization of Laboratory Animals." Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press, 2000.
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Microbial Status and Genetic Evaluation of Mice and Rats: PROCEEDINGS OF THE 1999 US/JAPAN CONFERENCE
In laboratory animal science, hybrid animals are usually obtained by mating among different inbred strains. They include the following four types: F1 hybrid, F2 hybrid, three-way cross, and four-way cross.
As explained subsequently in Genetic Test Method for Genetic Composition, genetic control of hybrids is easy, and it is possible to produce hybrid colonies with a high degree of reproducibility. Hybrids are considered appropriate for animal experiments because they generally show excellent reproductivity and good health, which compensate for the defects of their inbred parent strains such as low productivity due to inbreeding degeneration and various physiologic and biochemical defects caused by mutant genes. Historically, however, there have been few examples of the widespread use of hybrids in animal experimentation.
Closed colonies of rats and mice have long been used as representative species in experiments such as toxicity tests. Gene polymorphism is maintained in closed colonies, and the genotypes of individual animals are known to differ based on genetic testing (Katoh and others 1998). In this respect, closed colonies correspond to human populations; however, it is evident from an understanding of the origins of closed colonies that they cannot always be considered representative of species such as mice and rats. The main reason is that a single population (colony) does not possess all of the genes or gene polymorphisms of the species. There is also a strong possibility that closed colonies will lose their genetic stability because of artificial (human) control. Extreme phenomena (the bottleneck effect) concerning the number of members of colonies associated with microbiologic cleaning, in particular, are likely to occur during cesarean section, and we have experienced several actual examples of this.
SAFETY STUDIES AND LABORATORY ANIMALS
Studies in Which Animal Species Present a Problem
Mice and rats are widely used in new drug development, especially in toxicity (acute, subacute, and chronic) tests. In these studies, the responses are strong as long as the genetic differences in the same species are negligible. The doses are high, and individual differences or strain differences are not likely to appear. Although they are not performed at this time, studies formerly used the LD50 (50% lethal dose; the amount or concentration that causes death of 50% of the animals when a drug is administered) as the parameter. Therefore, primarily closed colonies, rather than inbred animals, have been used historically in this