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hampered by the fixation of large amounts of the rat genome across all outbred stocks, compared with natural populations and perhaps humans.


Currently, approximately 75% of all rats and mice produced commercially (at least in the United States) are noninbred. Although inbred strains have the most prominent role in transgenic and knockout animal development, here too outbreds are still used for a number of applications. Worldwide, pharmaceutical and contract research organizations consume more than 70% of all commercially produced laboratory animals including rats. Because this demand will likely continue, we need to manage and genetically monitor outbred animals and, in particular, outbred rats correctly.

With proper management as the target, there are several things to remember. As mentioned by other speakers, random genetic drift occurs in outbred populations. Over time, two populations starting with equal gene frequencies of alleles arbitrarily designated as capital A and lower case a will undergo random genetic drift. Eventually, one population may develop an increasingly greater proportion of a single allele, A, and after many generations that allele may become fixed in that subpopulation while the other subpopulation may continue to segregate until such time as the proportion of one or the other of these alleles increases and also becomes fixed.

One of the goals of this meeting has been to consider how to use genetic monitoring and allele frequencies to assess subpopulations for the purpose of determining relatedness and presumably for management interdiction. At Charles River, as elsewhere, we began evaluating subpopulations of outbreds using biochemical markers. As expected, we have seen that many of them are monomorphic. We surveyed the three populations of Wistar Han rats, as shown in Figure 1 and Figure 2, using biochemical and immunologic markers. These populations were from unrelated commercial breeding facilities and represented different sources and dates of acquisition of breed stock. Although some differences do exist, there is striking similarity between the frequency of biochemical and immunologic phenotypes among all three populations. Existing differences are not consistent between subpopulations.

In trying to judge the similarity of two populations based on the distribution of a single marker, one can easily overlook contradictory information if all of the other makers are not considered. Even if a panel of markers is used, judgments regarding the similarity of populations will be limited by which markers are surveyed. The assumption that some standard panel of markers that can easily fingerprint populations for the purposes of authenticating them, as is done with inbred or F1 hybrid animals, does not consider the possibility that the distribution of phenotypes for any given marker can change over time even when comparing populations that are considered to be closely related.

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