BioProject

Mouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. More...

Mouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight-strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well-defined brain tissue (the hippocampus). We identified substantial strain-specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large-scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found for Comt, a gene known to be involved in aggression. Keywords: mouse, inbred strains, hippocampus, genetic comparison Overall design: Total hippocampal RNA was extracted from eight inbred strains of mice and pooled within each strain (six mice/pool, one pool/strain). cDNA samples (eight) were prepared from the total hippocampal RNA and cRNA was prepared twice from cDNA. (Samples labelled 1 & 2 for each strain were from the first cRNA synthesis preparation, samples labelled 3 & 4 for each strain were from the second cRNA synthesis preparation).Each set of cRNA samples (16 in total) were then hybridized in duplicate to the Murine Genome U74Av2 Array (Chip A; Affymetrix, Santa Clara, USA). In total, 32 arrays were used; four arrays (two arrays with cRNA sample replicates in duplicate) for each of eight strains. Less...