For some researcher’s purposes, the purchase of the appropriate strain of rat from a reputable supplier will be sufficient for the work that needs to be accomplished. This includes both inbred strains and outbred stocks. For other experimental protocols, founder stocks may be acquired from suppliers or other researchers, and these founders will be used to generate local supplies of the animals. Further cross-breeding or other manipulations may also be performed, and those stocks may also need to be maintained and propagated appropriately. Before performing your own breeding, you may want to explore the existence of suitable strains to see if they meet your needs. Check out the Acquiring Rat Cancer Models section for existing models. A particularly useful resource for researchers seeking rat cancer models and links to related information may be the Cancer Portal at the Rat Genome Database (RGD).
Simple breeding schemes
Assuming the researcher wants to work with a genetically homogeneous population of animals for their research, the simplest strategy is to work with an inbred rat line. Inbred lines are generated by a founder pair of parental rats, with subsequent matings of the offspring siblings, for a total of 20 generations. Many inbred strains are available and in active use.
Keep in mind, though, that it may be wise to survey the genomes of the inbred animals periodically. Unanticipated changes may arise over time and can be propagated through the stocks. This can include active transposition activities, or by other variations such as copy-number changes.
Complex breeding schemes
A variety of breeding plans are employed to obtain the appropriate genetic composition of research rats. This can involve tracking single genes or genomic regions, or involve complex multi-allelic crosses that combine multiple genes or regions of interest. Sometimes this is to create a standardized background with desired characteristics or susceptibilities. Sometimes to isolate or combine desired traits. Sometimes researchers will want to compare traits or responses between strains. These schemes may involved naturally-occurring strains and lines, or may involve transgenic rats. The goals of the experiment will determine the particular breeding strategy required.
Backcrossing to parental strains is one mechanism. Intercrossing with different inbred strains may be desired, and this can lead to the generation of new recombinant inbred lines if propagated for 20 more generations. Randomized matings among multiple inbred strains for heterogeneous stocks may also be performed. Isolation of a specific chromosome (called consomic breeding) or genomic segment (congenic breeding) to create certain lines by backcrossing to inbred lines have been successful. Genotyping and characterizing the strains will be crucial to researcher’s understanding of the outcomes. For more details on characterizing rat strains examine the Characterizing Models section.
At the level of an individual gene or multiple genes desired in a certain context, the possibilities are nearly limitless. One can imagine scenarios that require multiple transgenes, or combinations of a transgene and a knockout, conditional expression strategies, or cases where adjacent genes on the same chromosome need to be segregated. This will require a study of the possibilities, and a detailed scheme to obtain the outcome. Offspring would need to be carefully examined, and researchers should be aware that some combinations could prove particularly challenging to develop if embryonic lethality becomes an issue.
The strategy to generate and maintain the appropriate strain depends on the goals of the research. In any case, accurate record keeping is crucial. For more details on record-keeping strategies, explore the rat husbandry section.
A final note about the naming of rat strains is in order. For the benefit of researchers who rely on the animal models, and for accuracy in the databases that store strain information, it is crucial that researchers adhere to the standards of strain and gene nomenclature. Journals frequently require the use of approved nomenclature for strains being reported. For the appropriate nomenclature, please consult the guidelines of the Rat Genome Nomenclature Committee, and the nomenclature and strain resources at the Rat Genome Database (RGD). The RGD team works with both the HUGO Gene nomenclature team for human genes, and the mouse nomenclature group as well to coordinate and standardize strain and gene name conventions, and joint nomenclature guidelines have been developed. Assistance in determining the correct nomenclature for rat strains is provided by the rat nomenclature team.