We propose to develop a new and powerful combined genetic and information research tool to further enhance the utility of the mouse as a model organism for understanding human biology. This is a set of 22C57BL/6J-Chr#PWD consomic (chromosome substitution) strains, in which each strain carries a single different chromosome from the PWD inbred strain on a C57BL/6J (B6) genetic background. Recent observations indicate that much of the genetic variation among inbred mouse strains derives from the contributions of the two subspecies Mus musculus domesticus and M. m. musculus suggesting that introgressing the chromosomes of one of these subspecies into the other would capture most variation among common strains, providing a """"""""universal set of consomics"""""""". The set of consomic strains that is nearing completion in the Czech Republic comes close to this ideal because the chromosomes of PWD, a pure M. m. musculus strain, are being introgressed into the B6 background, which is 80% M. m. domesticus. We will import these strains into The Jackson Laboratory, make them widely available, and characterize them for a range of physiologically important phenotypes and deposit the resulting information in the existing Mouse Phenome Database. The phenotypes include growth and fertility, sleep disorders, lung function, kidney function, obesity, diabetes, atherosclerosis, gallstones, hematology, osteoporosis, neurological function, immunologic function, hearing, sight, learning, memory, and aging. Phenotyping this consomic set will immediately identify chromosomes that contain genes affecting specific traits of biomedical interest. These data and this set of mice will provide a variety of mouse models to the scientific community that can be used to further explore the genetic basis of complex diseases and phenotypes. The post-genomic challenge of linking genotype and phenotype will require broad-scale, systems-wide approaches and infrastructure. We suggest that the availability of these consomic mice characterized for many phenotypes will help to meet that challenge. ? ?
