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Breeding Mice

For some researcher’s purposes, the purchase of the appropriate strain of mice from a reputable supplier will be sufficient for the work that needs to be accomplished.  This includes both inbred and outbred stocks of mice.  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.  Explore the Acquiring Mouse Cancer Models section for some sources of existing models.

A useful manual on this topic has been published by The Jackson Laboratory: Breeding Strategies for Maintaining Mice Colonies. Awareness of the biology of the mouse, including features of the estrous cycle and detection of pregnancy, the gestation time, and the developmental program and weaning time of the particular strain will be necessary, as it may vary slightly between backgrounds.

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 mouse line.  Inbred lines are generated by a founder pair of parental mice, with subsequent matings of the offspring siblings, for a total of 20 generations.  Many inbred strains have been developed and recorded, and the pedigree of many of them can be examined.  As described in a review of mouse models, these mice are then suited to many tasks:

— as a starting point for further model development

— as progenitors for further complex crosses

— for compound or drug testing

— as strains for subsequent mutation screening

 

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 mice.  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, to isolate or combine desired traits, or sometimes researchers will want to compare traits or responses between strains.  These schemes may involved naturally-occurring strains and lines, or may involve transgenic mice. The goals of the experiment will determine the particular breeding strategy required.  The classic text by Silver called Mouse Genetics provides an excellent foundation for the complexities encountered in breeding systems.

Numerous types of crosses are possible, depending on the genetic composition of the desired offspring. 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. Additionally precise breeding methods to pinpoint small segments and develop near-isogenic mice, or for recombinant introgression strains, are also known. 

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.

Genotyping and characterizing the strains will be crucial to researcher’s understanding of the outcomes.  Monitoring and preserving the strain may be necessary.  For more details on characterizing mouse strains examine the Characterizing Models section.

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 mouse husbandry section.

Nomenclature

A final note about the naming of mouse strains is in order.  For the benefit of researchers who rely on the animal models, and for accuracy in the databases that store mouse 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 mouse strains being reported.  For the appropriate nomenclature, please consult the guidelines of the International Committee on Standardized Genetic Nomenclature for Mice, and the official resources for mouse nomenclature at The Jackson Laboratory. The Mouse Genome Informatics (MGI) team works with both the HUGO Gene nomenclature team for human genes, and the rat 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 mouse strains is provided by the mouse nomenclature team.