Will a drug that makes a mouse less fearful be an effective treatment for people with anxiety? With 80 million years of evolution separating mouse and human brain development, some question the effectiveness of mouse models of human disease. For the mouse to be a good model of the human, gene expression would ideally be similar in the mouse and human brain. Now Strand et al. report conservation of region-specific gene expression in mouse and human brain in a recent article in PLoS Genetics.
The authors did parallel analyses of regional gene expression in the human and mouse brain. They used microarrays to determine gene expression in motor cortex, caudate nucleus and cerebellum in humans and anterior cortex, striatum and cerebellum in mice. Mice and humans showed similar regional differences. For example, cortex and striatum differed by 26% in mouse and 27% in human.
Similar groups of genes showed the most regional expression differences in mice and humans. The authors compared human and mouse lists of the 100 most differentially regulated genes in cortex and cerebellum. Only 9 genes did not match. Of the top 250 genes most differentially regulated in caudate and cerebellum, only 39 genes were different in mice and humans.
The pattern of gene expression varied more across tissues than between species. Region-to-region differences were the greatest source of variability for 89% of human and 85% of mouse genes. When the authors rank-ordered human genes by region-to-region variability, the genes clustered according to brain region, suggesting that such variability is an appropriate measure of tissue specificity. They also clustered mouse genes according to brain region when they arranged them by the rank-ordered list of their human homologs, suggesting that tissue specificity is similar for homologous genes. The authors designated a point in space for genes expressed in mouse and human cortex, striatum and cerebellum. In all cases, the shortest line linked the same brain region in different species (mouse cortex–human cortex), suggesting that gene expression is more similar across than within species.
Region-specific genes are evolutionarily conserved. The authors binned genes by regional variability. Genes with the highest variability showed the most identity across species.
Many human diseases have transcriptional signatures. Because of the similarity in regional patterns of gene expression across species, the authors suggest that transcriptional signatures should be used to phenotype mouse models of human disease.