Given that there is substantial, and economically important, genetic variation in humans in response to xenobiotics and that rats are widely used in toxicology and pharmacology, the failure to seek genetic variation in rats, which could be used as a model of similar conditions in humans, is surprising. Unless toxicologists change their research tactics they will fail to benefit from the enormous advances currently being made in molecular genetics.
It is now 20 years since ILAR published an excellent set of guidelines on “Laboratory Animal Management: Genetics” (ILAR 1979). These guidelines described the main types of strains and stocks then available to research workers, which included inbred strains and their derivatives such as congenic strains and recombinant inbred strains, mutants, and “stocks not genetically defined,” including outbred stocks.
In a discussion of the choice of inbred strains versus outbred stocks, the guidelines suggest, “An investigator working with species for which inbred strains are available would be well advised to use them. ” The serious limitations of genetically undefined strains were emphasized. Although such animals may be cheaper, they will be phenotypically more variable so that larger numbers are needed, they are subject to genetic drift, and colonies with the same name from different breeders may differ to a serious extent. Moreover, since that time there have been many papers published that describe the valuable properties of inbred strains and the limitations of outbred stocks (Festing 1990, 1995, 1997a,c; Festing and Wolff 1995). Yet, outbred stocks continue to be used widely, even though no scientific justification for their continued use appears to have been published in the last 20 years.
In contrast, inbred strains, which have been described as “immortal clones of genetically identical individuals,” tend to be highly uniform, they stay genetically constant for long periods, the genetic and phenotypic characteristics of most strains are well documented, and genetic quality control is relatively easy using DNA genetic markers (Festing 1997b).
Genetic variation in response to xenobiotics is seen most clearly as strain or stock differences, in experiments that have used more than one strain (for convenience the term strain will be used to indicate both inbred strains and outhred stocks). Examples include differences in response to DMBA among three rat strains in which strain COP was totally resistant to a dose of carcinogen that caused 100% mammary tumours in WF, with F344 being intermediate (Moore