IGS Program for Mice and Rats
Our IGS program ensures that animals bred at any global production facility have the same genetic profile if they are an inbred strain or the same relative level of genetic heterogeneity for an outbred stock.
Outbred Mice and Rats
For outbred stocks, genetic drift and colony divergence across multiple generations for strains bred in isolation can be expected among rodent colonies. While genetic drift is natural and unavoidable, it’s important to maintain diversity at the individual level and standardize the rate of genetic variation across multiple colonies that are geographically separated. For outbred stocks, the IGS program ensures minimal inbreeding, heterozygosity, and management of genetic drift across colonies worldwide.
Fig. 1: A key element in the genetic management of outbred stock is migration. Every 3–5 years (10 generations), animals from the foundation colony are migrated on a rotational basis to production colonies to replace some breeders.
Fig. 2: Every year, animals are migrated back into the foundation colony from production colonies to replace 5% of the foundation breeding pairs. This system of forward and backward migration acts as a "genetic glue" that links all colonies and ensures that none diverge far from the others. The result is all colonies are genetically merged into one large colony which resides in multiple locations around the world.
Inbred strains are defined as animals produced by a minimum of 20 generations of brother-sister mating, traceable to a founding pair. We use a pyramid mating system coupled to a foundation colony for inbred mice strains across the world. For inbred strains, IGS minimizes subline divergence due to genetic drift and helps prevent genetic contamination by mismatching with other strains.
Fig. 3: We use a pyramid mating system coupled with a foundation colony for all inbred strains. In this system, the foundation colony serves as the genetic and health standard and provides breeders for the top level of the pyramid in every barrier room. The unidirectional flow of breed stock in this system helps to ensure that any genetic changes or mutations, which would be more likely to occur in the larger expansion or production colonies than in the smaller nucleus colony, will "wash out" within a single generation.
Frequently Asked Questions About the International Genetic Standardization (IGS) Program
What is genetic drift?
Genetic drift is the spontaneous changes in genomic DNA that can occur in any mouse or rat breeding colony and can negatively affect research reproducibility. It can be minimized through colony management best practices, accurate strain nomenclature, and substrain designation.
What impact does genetic background have on the reproducibility of research?
The complexity of biological systems researchers study is a key factor impacting research reproducibility. For studies employing transgenic rodent lines, a lack of understanding of genetic backgrounds, as well as genetic drift, genetic contamination, and genotyping inconsistencies all contribute to the issue of reproducibility in mouse studies.
How can I refresh breeder colonies to maintain the genotype of a mutant strain?
Refreshing breeder colonies is an important requirement and should be performed on regular basis (every 5 – 10 generations of breeding). This will help mitigate the risk posed by genetic drift and occurrence of spontaneous mutations that may impact mouse phenotypes and experimental data bias.
Refreshing can be done in two ways. The first pertains to revitalizing cryostock. Cryopreservation should be done when we can be confident that the line has not already drifted. The second would be to breed a few generations (three are recommended) with wild-type animals purchased from genetically controlled colonies. Don't forget to breed transgenic females with WT males at first to refresh the Y chromosome.
Why are inbred mice commonly used in research?
Inbred and F1 hybrid strains are frequently the mouse models of choice for research because of their unique and stable phenotypic traits, and hence, uniformity, and their predictable experiment response.