Recombinant congenic mice
List of Recombinant Congenic Mice
Definition
The standard procedure for generating a set of recombinant congenic (RC) strains is to mate mice of two genetically distinct inbred strains, backcross their descendants to one of the parental strains (the recipient) for two generations, then initiate sister x brother inbreeding, without selecting for particular markers or phenotypes. On average, the recipient contributes the greater proportion (87.5%) of the genome to each RC strain constructed by this standard approach.
Not all RC strains are produced by this standard method. The number of backcrosses may vary, resulting in different genomic proportions derived from the recipient. Selection may occur for either donor or recipient alleles. Other breeding variations may be particular to entire RC strain sets or to individual strains within a set. In any case, because backcrossing increases homozygosity twice as fast as does sibling mating, an RC strain is considered inbred when the sum of the number of inbreeding (F) generations plus twice the number of backcross (N) generations (including the initial cross) is at least 20.
Applications and Selection Criteria
RC strains are a valuable resource for analyzing complex traits. The relatively small proportion of the donor genome serves as a unique tool in the genetic dissection of a complex trait. RC strains homozygous for donor alleles at two or more interacting loci (or secondary RC strains derived from crosses between RC strains) are used to study gene interactions. An RC panel developed by Dr. Edward Leiter of The Jackson Laboratory combines QTLs (which alone contribute small phenotypic changes) in such a way as to provide an improved model for human type 2 diabetes (Reifsnyder et al. 2002). An RC strain can also be used as a donor in constructing a single-locus congenic strain on a recipient background.
In general, it is best to select RC strain sets whose progenitors differ significantly with respect to the trait(s) of interest. However, as is true for RI strains, RC strain sets with progenitors whose trait(s) of interest do(es) not differ significantly are also informative, especially for analyzing complex multigenic traits. Interactions between host and recipient alleles at different loci can produce phenotypes outside the ranges of the parent strains. These subsets can then be analyzed by performing crosses involving the affected strains.
Recombinant Congenic Strain Nomenclature
An RC strain is designated, without intervening spaces, by the abbreviation for the recipient, a lower case “c,” the abbreviation for the donor, an Arabic numeral designating the strain’s number within the set, a forward slash, the Registration Code of the scientist who produced the strain, the Registration Code of subsequent holders (if a substrain) and the Registration Code for the laboratory that maintains and distributes the strain. For example, NONcNZO5/LtJ is the fifth member of an RC strain set derived from a cross between NON/ShiLtJ and NZO/HlLtJ, developed by Edward Leiter (Lt), and maintained and distributed by The Jackson Laboratory (J).
Handling and Care
RC strains are maintained as inbred colonies (by sibling mating) and generally do not require any special husbandry. Reproductive performance may vary among strains within a set.
Reference
Reifsnyder PC, Leiter EH. Deconstructing and Reconstructing Obesity-Induced Diabetes (Diabesity) in Mice. Diabetes 2002; 51:825-832.
