de Jong S et al. BMC Genomics 2010, 11:20 http://www.biomedcentral.com/1471-2164/11/20 R E S E A R C H A R T I C L E Open Access Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background Simone de Jong S1, Tova F Fuller2, Esther Janson1, Eric Strengman1, Steve Horvath2,3, Martien JH Kas4, Roel A Ophoff1,2,5* Abstract Background: We performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J. The selected brain areas are implicated in neurobehavioral traits while these mouse strains are known to differ widely in behavior. Consequently, we hypothesized that comparing gene expression profiles for specific brain regions in these strains might provide insight into the molecular mechanisms of human neuropsychiatric traits. We performed a whole-genome gene expression experiment and applied a systems biology approach using weighted gene co-expression network analysis. Results: We were able to identify modules of co-expressed genes that distinguish a strain or brain region. Analysis of the networks that are most informative for hippocampus and amygdala revealed enrichment in neurologically, genetically and psychologically related pathways. Close examination of the strain-specific gene expression profiles, however, revealed no functional relevance but a significant enrichment of single nucleotide polymorphisms in the probe sequences used for array hybridization. This artifact was not observed for the modules of co-expressed genes that distinguish amygdala and hippocampus. Conclusions: The brain-region specific modules were found to be independent of genetic background and are therefore likely to represent biologically relevant molecular networks that can be studied to complement our knowledge about pathways in neuropsychiatric disease. Background Genome-wide gene expression profiling has been used to aid in the discovery of genes involved in human dis- eases and to discriminate between disease subtypes. This approach has already been successfully applied in cancer and obesity research [1,2], but similar approaches have not yet been widely applied to human neuropsychiatric traits. An important issue concerning expression profil- ing in these disorders in man is the lack of the most relevant tissue, i.e. the brain, for study. Except for lim- ited numbers of post-mortem samples, there is no easy * Correspondence: r.a.ophoff@umcutrecht.nl 1Department of Medical Genetics and Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands access to human neuronal tissue for expression studies [3]. Mouse models, however, have long been used to study neuropsychiatric traits. There is consensus that symp- toms of disorders such as major depression and anxiety can be studied by observing behavior in inbred strains [4,5]. Moreover, mouse brain tissue is accessible and most brain regions are highly conserved between mouse and human [6,7]. Regional gene expression in the brain has been shown to be conserved between non-human primates, rodents and man, making it possible to study mice in relation to human neurobiology [8,9]. This study focuses on two brain regions, the hippo- campus and amygdala, because of their importance in neural behavior and psychiatric disease. These areas are both part of the limbic system and known to be heavily © 2010 de Jong S et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.