Properties of inbred strains and outbred stocks, with special reference to toxicity testing

Genetically uniform or isogenic strains (inbred strains and F1 hybrids) have a number of properties that make them valuable in toxicity testing, provided the experimental design can be modified to include more than one such strain. Isogenicity and homozygosity lead to great phenotypic uniformity, high long-term genetic stability, high identifiability, large differences between strains (individuality), and the possibility of setting up daughter colonies genetically identical to the parents. This in turn means that many isogenic strains are internationally distributed, and that considerable background data exist on the characteristics of the common strains. Toxicity testing usually involves the calculation of dose-response curves. Use of phenotypically variable nonisogenic stocks reduces the precision with which such curves can be estimated, without many other benefits. A single isogenic strain may not be satisfactory as it may be resistant to the drug being tested. However, the use of several isogenic strains with a factorial experimental design would overcome this problem, would give high statistical precision, and would provide a better basis for extrapolation to humans than the use of a single stock. Such a design would make it possible to choose a range of strains on the basis of known drug sensitivities, it would be highly repeatable, it would allow comparison of different drugs, and it would show whether the response was genetically determined. The benefits of such an experimental design far outweigh the disadvantages, which are mostly of a practical nature.