Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background.
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.
de Jong
Simone
S
Department of Medical Genetics and Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Fuller
Tova F
TF
Janson
Esther
E
Strengman
Eric
E
Horvath
Steve
S
Kas
Martien J H
MJ
Ophoff
Roel A
RA
D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D016000:Cluster Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics*; D008810:Mice, Inbred C57BL / Q000235:genetics*; D008957:Models, Genetic; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013045:Species Specificity