Recombinant inbred (RI) strains are a powerful tool for the analysis and mapping of complex traits of biomedical significance. The largest existing set of RI strains, a 45-strain set derived from C57BL/6J and A/J, is in danger of being lost. These strains are of special importance to biomedical research because the progenitors differ in atherosclerosis, diabetes, obesity, gall stone formation, cancer, birth defects, and susceptibility to over 30 infectious diseases including herpes, leprosy, and tuberculosis. We propose to import this animal genetic resource into The Jackson Laboratory, to permanently preserve each strain by freezing 1,000 embryos, and to provide mice to other investigators. To facilitate the use of these RI strains, we will distribute DNA from each strain, Southern blots of progenitor DNA cut with 10 restriction enzymes to aid in the search for polymorphisms and Southern blots of DNA from the entire RI set to facilitate the search for linkage. Although this is primarily a resource grant, we will characterize this RI set further by analyzing genetic differences between the progenitors in diseases induced by a high fat diet, such as atherosclerosis, obesity, diabetes, and gall stone formation. We will type additional strategically located DNA markers in this RI set so that no genetic marker is more than 20 cM from another. When this goal is accomplished, this RI resource can be used to rapidly and efficiently map any new gene polymorphic by simply determining the strain distribution of the alleles among the RI strains, between the progenitors. We propose an Informatics Center that will include all RI strain sets. The components of this Informatics Center will be a Macintosh computer program, RI Manager, readily available to all investigators, continuously updated strain distribution patterns from the current literature available on computer disk, and semiannual publication of a booklet with the strain distribution patterns of all RI strain sets, similar to the information booklets currently released periodically by The Jackson Laboratory on human-mouse homologies, mouse DNA probes, and the mouse genetic map.
