GeneChip analysis of hippocampal gene expression profiles of short- and long-attack-latency mice:Technical and biological implications

To gain insight into the molecular mechanisms underlying the behavioral differences between two mouse lines genetically selected for long and short attack latency (LAL and SAL mice, respectively), we have recently applied the large-scale gene expression profiling method known as serial analysis of gene expression (SAGE) to generate hippocampal gene expression profiles of these mice. The aim of the present study is to extend and validate the SAGE expression profile of hippocampi of LAL and SAL mice using GeneChips (Affymetrix, Santa Clara, CA; one array per mouse, n = 5 per mouse line). As was the case with SAGE, GeneChips detect only medium- to high-abundance genes in the hippocampus. Extensive analysis of GeneChip data using very stringent parameters shows differential expression of 122 genes, all except one of which were expressed at higher levels in LAL mice (P <0.01). As predicted by SAGE, our data indicate higher expression of several cytoskeleton genes in LAL mice, suggesting longer axonal and dendritic projections in the hippocampus of these mice. This is consistent with our tentative model, in which the behavioral differences between LAL and SAL mice may be related to structural differences in the hippocampus. In addition, a group of 76 genes with diverse biological function and 46 expressed sequence tags (ESTs) were all expressed at higher levels in LAL mice. A novel finding in this study was the significantly lower expression of only a single gene, growth arrest-specific gene (gas5), in LAL mice. As gas5 does not encode a protein but several small nuclear RNAs, our data suggest that small RNAs may contribute to the molecular mechanisms underlying the extreme behavioral differences between LAL and SAL mice. (C) 2003 Wiley-Liss, Inc.