Research Uses

Outbred stocks continue to be widely used, even though for those species where there is a choice (mainly mice and rats), there is a compelling case for preferring isogenic strains.11,12 For other species, there is generally no practical alternative. (The term "stock" is used for outbred colonies, with the term "strain" being reserved for isogenic strains, although in this chapter, in some cases, the term "strain" will be used collectively to mean all genetic types. The context should make it clear in which sense the term is being used.)

These animals have some advantages. They are cheaper to buy or breed, partly because they are more prolific than isogenic strains and partly because there are fewer outbred stocks, so they can be bred on a large scale with relatively less wastage. As a result, they tend to be more readily available in groups of a defined weight or age range.

The disadvantages are that each animal is genetically unique, so there is no information on the genotypes of individuals unless each is specifically genotyped. Phenotypic variation is usually greater than is found with isogenic strains, as individuals differ due to genetic and nongenetic factors. This means that more animals are usually needed to achieve a given level of statistical precision in a controlled experiment than if isogenic animals had been used. Also, stocks are subject to genetic change as a result of inbreeding and directional selection. Over a period of many generations, outbred mice and rats have tended to be selected for increased body size, so are often larger than their isogenic counterparts. Genetic change can occur rapidly over a period of a few generations, and this may mean that background data on the phenotypic characteristics of the stock may quickly lose its validity. In particular, there is good evidence that colonies with the same name such as "Wistar" rats are often genetically different. This can cause difficulties for people needing to replicate other people's work, as nominally identical animals may in fact be genetically distinct. Unfortunately, methods of genetic quality in outbred stocks are undeveloped. It is not even possible to distinguish between Wistar and Sprague-Dawley rats using known genetic markers.

Outbred stocks are mainly used in general research for studies using species in which there is no isogenic alternative, studies where genotype is judged to be of little importance, in noncritical studies, and in cases where the research worker is unaware of the advantages of isogenic strains. They are widely used in toxicological testing, though their use in such studies has been questioned.13,14 Where animals of a broad range of genotypes are wanted, it is much better to use small numbers of isogenic animals of several strains rather than outbred animals of a single stock. However, they are suitable for within-animal experiments, such as crossover experimental designs or those comparing left and right sides, as in this case, precision is not affected by differences between animals. They may also be suitable for experiments requiring sources of live tissue and for the maintenance of parasites, assuming host-parasite relationships are not of interest. They continue to be widely used in neuroscience, though this may be due more to ignorance of the advantages of isogenic animals, rather than any good scientific argument for their continued use. A discussion of the relative merits of isogenic and nonisogenic stocks in aging research, which is relevant to many other fields of research, is given in Miller et al. (1999) and Festing (1999).1115

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