Genome-wide analysis of kainic acid-induced gene expression in dentate gyrus from CTR and SRF knockout mice

To identify genes regulated by SRF in response to increased neuronal activity whole-genome expression profiling (Illumina Mouse WG-6 microarrays) of kainic acid-induced genes were performed. We found that loss of SRF in DG leads to specific deficits in activity-induced gene expression. Identified genes functions are associated with synapse plasticity, epilepsy, outgrowth of neurites, behavior and MAPK signaling pathway. The microarray experiment was performed to identify SRF-dependent activity-induced genes, using brain-specific, inducible SRF gene knockout mice. Conditional mutants of Srf were obtained by crossing mice in which Srf gene was flanked by loxP sites (Srf f/f) with an CaMKCreERT2 line to ablate its expression exclusively in excitatory forebrain neurons. Knockouts (KO = Srf f/f;CaMKCreERT2) and control littermates (CTR = Srf f/f) were used in the experiments. To enable time-specific induction of SRF deletion, adult mice, were injected with tamoxifen. Global gene expression induced by kainic acid (KA, 35-50 mg/kg) was analyzed. At 6 hours after seizures induction (seizures severity 5; according to modified Racine scale) or saline injection, CTR and KO animals were sacrificed and dentate gyrus was microdissected and used for RNA isolation. In order to identify SRF-regulated genes, we used Illumina MouseWG-6 v2.0 Expression BeadChips.