SPECIAL MOUSE STRAINS RESOURCE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Many common inherited human diseases are genetically complex; that is, they result from the interaction of more than one gene. Examples are diabetes, cardiovascular diseases, cancer, obesity, and asthma. Even genetically "simple" single mutation diseases are frequently modulated in severity by secondary genes. The advances in positional cloning and candidate gene analysis have led to relatively rapid identification of the genes underlying many human and mouse disorders caused by single gene mutations. Similarly, the goal of genetic analysis of genetically complex diseases is to discover the underlying genes with the ultimate goal of prevention or therapy. Genetic analysis of complex traits requires model systems in which genetic manipulations can be carried out. The metabolic, organ/tissue, and genetic similarities between mice and humans and the ease with which the mouse can be genetically manipulated make mice the obvious model for many of these complex human diseases. Linkage crosses for complex trait analysis, however, are time-consuming and expensive. We propose to fund with this grant a resource of special mouse strains that are valuable tools for complex trait analysis and whose use will improve the efficiency of identifying genes in mouse models of human multigenic diseases. The Special Mouse Strains Resource (SMSR) will contain six Recombinant Inbred (RI) strain panels, a set of 21 Chromosome Substitution (CSS) strains, and multiple Congenic strains. The RI and congenic strains are already at The Jackson Laboratory but are in need of partial support to continue to maintain them in breeding colonies. The CSS strains will be imported from Dr. J. Nadeau, Case Western Reserve University. To enhance the value of the strains we will 1) increase the number of DNA markers genotyped in the RI strain sets to improve their value for genetic mapping, 2) define more precisely the extent of differential segments in the congenic strains to improve their value for genetic mapping, and 3) phenotype the CSS strains to improve their baseline characterization. We will also develop a database of phenotypic information on the RI, CS, and congenic strains covered by this grant and a graphic map of the distribution and extent of differential segments in the congenic strain set.