RAT GENE EXPRESSION ANATOMY

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This R01 application is submitted in support of a PGA entitled "Expression Profiling of Rodent Models of Human Disease." The theme of the application is "Examining Gene/Environment Interactions in Rodent Models of Human Disease Using cDNA Microarrays" to link phenotype to genotype. In support of that application, we will establish a Rat Gene Expression Anatomy Component and propose to take advantage of a novel and powerful approach that dissects multigenic traits through the use of chromosomal substitution strains of rats (consomic rats). A consomic rat has a full-length chromosome from one inbred strain (e.g. "diseased pathogenic" strain) introgressed onto the background of another inbred strain (e.g. "resistant" strain). Hence, the contribution of genes residing on each of the 22 rat chromosomes (20 autosomes, X, Y) to heart, blood and lung functions can be assessed by phenotyping and expression profiling a panel of 22 consomic rat strains. Microarray analysis of consomic rats offer an unprecedented means to link complex gene expression profiles to pathophysiological pathways. Comparisons between the consomic strains will provide valuable insights into the genomic pathways ("clustered" gene expression patterns) that differ between strains and how these differences might be connected to a particular pathogenic phenotype of the animal. The ability to: (l) link biological functions of the heart, blood and lung systems to genomic expression data, (2) develop a national database as a resource that archives the expression data, and (3) provide a program that teaches researchers how to apply this information to their own R01 research programs provide an invaluable resource to the research community.