In science it can be important to have as much
homogeneity as possible for certain experimental situations. In the case
mice, it is quite straightforward to develop genetically identical mice
by inbreeding. These mice can be used
to replicate one’s own experiments over time, and to compare results
labs using identical mice.
Foundations of inbreeding
Inbreeding (systematic brother-sister matings) was a tactic used by “mouse fanciers” who kept mice as pets and who realized that they could maintain some of the prized traits among their mice by regular sibling matings. When researcher Clarence Little was exploring coat color inheritance, he used a cross of two mouse strains, but he observed in the mouse crosses that coat color inheritance was variable (heterogeneous). Little apparently realized that genetic studies of the sort that he had in mind would depend enormously on the development of inbred mouse strains in which he could assume genetic homozygosity. He began to experiment with systematic inbreeding of the progeny of a mouse cross to reduce this variability. He named the first inbred stock of laboratory mice DBA, and their foundational status can be observed in the pedigree of inbred strains. Offspring of the ancestral DBA mice are still available to researchers today. Today mice are considered to be stably inbred after 20 generations of the appropriate pairings.
Features of inbred mice
A strength of the laboratory mouse as a model system results from the availability of hundreds of inbred strains which harbor different characteristics, including some that are prone to develop specific types of cancers. Responses to experimental therapies can be quantified and assessed in a standard framework—that is, all the mice have an identical genetic background, and would be expected to generate similar responses to similar exposures and treatments. Accumulating data in standardized collections worldwide allow cancer researchers to investigate virtually any phenotype of interest, and to take advantage of the breadth and depth of knowledge on that model system.
Strategies employed by researchers
Further, an inbred strain may be cross-bred with another strain to develop new models. A variety of methods and strategies are used to develop the appropriate mouse genetic framework. These methods include:
- Recombinant inbred strains, which are utilized for mapping traits, are animals that have been out-crossed from two separate inbred strains, and then maintained for generations, are available and in wide use.
- Heterogeneous stocks, which are employed for increased precision for locating genomics segments of interest, are used because the variations between animals can be teased out from the background strain characteristics.
- Consomic strains, which an entire chromosome from one inbred strain replaces the corresponding chromosome in another inbred strain, and vice versa, are being successfully employed. From the consomic strains, researchers can rapidly breed congenic strains that carry only a small segment that differs between animals to narrow the region on a chromosome to a size that can be targeted for gene identification.
For additional technical details on generating or utilizing inbred mice, explore the Generating Inbred Mice area of this site.