Recombinant inbred mice

Definition

Recombinant inbred (RI) strains contain unique, approximately equal proportions of genetic contributions from two progenitor inbred strains. Traditionally, RI strains are constructed by crossing two inbred strains to produce an F1 generation, followed by 20 or more consecutive generations of brother x sister mating (Bailey 1971; Taylor 1978). However, the F1 generation may be produced in other ways, such as by crossing mice of existing RI strains, advanced intercross lines, or multiple inbred strains (e.g., an 8-way cross). If backcrossing to one of the parental strains occurs before inbreeding, a recombinant congenic strain is produced and should be named accordingly.

Because unlinked alleles segregate randomly in an F2 generation, parental and recombinant genotypes occur with equal frequency among a set of RI strains. Linked loci are more likely to be transmitted together.

Applications and Selection Criteria

As tools for mapping genes or identifying quantitative trait loci (QTLs), RI strains have a number of advantages over F2 and backcross populations:

  1. Being inbred, RI strains are perpetually renewable. A sacrificed mouse used to perform in vivo experiments can easily be replaced.
     
  2. Because an RI strain includes mice of both sexes, traits specific to either sex may be studied in the same strain.
     
  3. Because data acquired for an RI strain set are cumulative, researchers may compare their results with information published on the same set of strains.
     
  4. Because extensive genetic data and maps exist for most RI strain sets, mapping a newly characterized trait often requires no additional genotyping.
     
  5. QTLs mapped using RI sets can be quickly verified and refined by generating sets of either RI intercross (RIX) or backcross (RIB) lines between RI strains that have recombination in critical QTLs (RIX and RIB strains are also perpetually renewable and genetically defined).
     
  6. Data obtained from several RI strain sets may be compared or combined, particularly if the sets have a progenitor strain in common or are assorting for alleles of common origin in the genomic region(s) of interest.
     
  7. Because inbreeding beyond the F2 generation fosters additional opportunities for recombination between linked genes, a given number of RI strains can provide higher mapping resolution than can the same number of F2 mice.
     
  8. Finally, sequence data are available for the inbred strains from which most RI strains are derived, often allowing investigators to identify a specific allele responsible for a phenotype.

As with any genetic mapping resource, the greater the number of samples (in this case, RI strains in a set) used to analyze a trait, the more precisely the trait can be described. Thus large sets of RI strains offer obvious advantages over small ones. 

For most applications, it is initially best to select RI strains whose progenitors differ significantly for the trait(s) of interest. However, RI 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 parental strains. These subsets can then be analyzed by performing crosses involving the affected strains.

RI Strain Nomenclature

RI strains are designated, without intervening spaces, by the abbreviation of the female progenitor strain, an upper case letter “X,” the abbreviation of the male progenitor strain, an Arabic number indicating the RI line, a forward slash, the ILAR-assigned Registration Code of the scientist who developed the strain, and the Registration Code of the laboratory that maintains and distributes the strain. For example, AKXD1/TyJ is the first (1) RI line derived from a cross between an AKR/J (AK) female and a DBA/2J (D) male, was developed by Benjamin Taylor (Ty), and is now maintained and distributed by The Jackson Laboratory (J). All members of an RI set are serially numbered, regardless of how many laboratories produced them. Serial numbers may be obtained from Mouse Genome Informatics (nomen@informatics.jax.org).

Exceptions to this nomenclature format are made in three cases: 1) when an RI strain progenitor cannot be differentiated from another RI progenitor by an abbreviation of less than three letters; 2) when the paternal progenitor strain abbreviation ends in an Arabic numeral, in which case a hyphen is inserted before the individual strain number; 3) when members of an RI strain set have been identified for many years by capital letters rather than numbers.

Handling and Care

RI strains are maintained as inbred colonies (by sibling mating) and generally do not require any special husbandry. Reproductive performance may vary among individual strains within a set.

General Notes

As in other inbred strains, mutations may occur spontaneously and be bred by chance to homozygosity during propagation of RI strains. These may confound genetic analyses. As a preventative measure, many RI strains at The Jackson Laboratory are preserved as frozen embryos. Some RI strains breed poorly and are available only in small numbers. Finally, when RI strains are constructed, coat color alleles differing between the progenitors (and not necessarily having a visible effect in the progenitors) assort randomly. Thus, coat colors of mice from different strains within a set may vary. The coat colors of most RI mice are included in the strain details.

Additional information on RI strains can be found in The Jackson Laboratory’s “Macroarray Resource Manual,” obtainable by completing this request form.

References:

Bailey DW. 1971. Recombinant-inbred strains. An aid to finding identity, linkage, and function of histocompatibility and other genes. Transplantation 11:325-7.

Taylor BA. 1978. Recombinant inbred strains: Use in gene mapping. In: Morse III HC (ed), Origins of Inbred Mice. Academic Press, NY. pp. 423-438.