The Jackson Laboratory

Diversity Outbred and Collaborative Cross Mice to Offer Maximum Allelic Variation

JAX^® NOTES Issue 514, Summer 2009

In its quest to provide even more powerful genetically distinct mouse resources, JAX is developing a population of Diversity Outbred (DO) mice, designed to maximize allelic variation throughout the genome. Each DO mouse will be genetically unique, and groups of them will approximate the genetic diversity found in human populations. Unlike fully inbred strains, DO mice will have normal levels of heterozygosity, recapitulating that of humans. DO mice will enable researchers to rapidly map genetic loci at high resolution and identify individual genes involved in disease.

The DO mice are produced by a novel outbreeding strategy that maintains a balanced mixture of the founder genomes and avoids allelic loss and inbreeding. The DO founders are mice from the 160 breeding lines used to construct the Collaborative Cross (CC) (Chesler et al. 2008). The CC is a large panel of new inbred mouse strains derived from an eight-way cross using a set of JAX^® Mice that includes three wild-derived strains. The progeny of these crosses are currently being inbred to produce the new CC strains. Like the DO mice, the CC strains will considerably increase the mapping resolution possible through conventional crosses and provide new strains harboring a mosaic genome, with alleles from the eight founder strains (The Complex Traits Consortium 2004; Chesler et al. 2008).

The DO mice will be available from JAX as early as next year; the CC strains will be available in 2012. Both resources will greatly improve the ability to identify genes that modulate susceptibility to disease and drug resistance, critical steps in our progress toward realizing personalized medicine.

References

Chesler EJ, et al. 2008. The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics. Mamm Genome 19:382-9.