Definition and Development
Sets of RC strains are developed in a similar way to the development of RI strains, except that instead of inbreeding from the F2 hybrids, a few (generally about three) generations of backcrossing to one of the parental strains is done first, followed by sib mating of several independent lines for the equivalent of 20 generations.6 Each backcross generation is regarded as being equivalent to two generations of sib mating. If the F1 hybrid is designated generation N1, then backcrossing to N3 is typically used so that each strain has, on average, a 12.5% contribution from the donor strain and 87.5% contribution from the background strain. The set would then be regarded as fully inbred at N3F14. Other levels of backcrossing may be used, and this will be indicated in the description of each RC set.
The individual RC strains are designated by uppercase abbreviations of the strain names, with the recipient (i.e., background) strain designated first, separated by a lowercase "c" with numbers to indicate the individual lines. For example, one of the CcS set of RC strains with BALB/c as the recipient strain and STS as the donor strain could be designated CcS6 if it was the 6th of such a set of strains.
These strains are most useful for the identification and mapping of quantitative trait loci for characters, which differ between the donor and recipient strain. Assuming, for example, that a set of RC strains was developed from the N3 generation of a cross between two inbred strains, and that the character of interest (say a "high" or "low" response to a toxic agent in the donor and recipient strains, respectively) is controlled by several loci with different alleles in each of the two strains. For each locus, about 1/8 of the RC strains should contain the donor allele, and 7/8 of the strains should carry the background strain allele. The exact numbers will depend on chance sampling variation, so that there may be none, one, two, three, etc. of the strains with the donor allele, and some will have more than one. All strains are then phenotyped for the response to the toxic agent. If the response is due to a single locus, then most of the strains will have the response of the background strain, but a few may have that of the donor strain. If the character is controlled by several loci, then donor alleles will be present in a larger number of the strains, with a range of different phenotypes among the full set of strains. Most sets of RC strains have been genotyped at many marker loci, so that once a "high" strain has been identified, chromosomal regions, which are of donor origin, will already have been identified. Normally, one of the "high" RC strains will be crossed with the background strain. Segregation in the F2 generation will be studied for evidence that the difference is due to a single locus, resulting in Mendelian segregation. If this is the case, then one of the alleles for "high" response will have been trapped in the RI strain, and it can then be mapped and studied in more detail.
RC strains provide a powerful research tool, and they have been used in a wide range of studies, including susceptibility to cancer,48 pathogens,49 and bone strength,50 as a few examples. However, so far their use has been limited to a few laboratories that made the considerable investment in developing and genotyping some useful sets. The main disadvantage is that they can usually only be used for studying characters that differ between the two parental strains. Thus, if the phenotype of interest is not seen in either of the parental strains, it is unlikely (though not impossible) that a particular set of RI strains will be of use in investigating that character.
Once a set of RC strains is fully inbred, each strain is an inbred strain in its own right and should be maintained in the same way as any other inbred strain.
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