GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307928/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307928GEOGSEfalseMulti-modal transcriptomic analysis reveals conserved and divergent molecular mechanisms underlying behaviors in mouse models of schizophreniaSchizophrenia (SCZ) is a severe mental disorder with complex behavioral pathology and complex genetic risk. Here, we performed an integrated transcriptomic analysis of the prefrontal cortex in two distinct male C57BL/6 mouse models of schizophrenia, the neurodevelopmental methylazoxymethanol acetate (MAM) model and the acute non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 model, compared to that of human patients. Transcriptome in the MK-801 model displayed a modest correlation with that of schizophrenia patients, higher than the MAM model, underscoring NMDAR antagonism's relevance to the core pathology of the disorder. Using weighted gene co-expression network analysis, we identified fifteen co-expression modules across the mouse models, with eight modules significantly associated with schizophrenia-like behavioral endophenotypes. Notably, modules darkturquoise (linked to hyperlocomotion) and royalblue (associated with social withdrawal) were enriched in Wnt and PI3K/Akt signaling pathways, respectively. Pharmacological inhibition of these two pathways specifically rectified corresponding behavioral anomalies in the MK-801 model, highlighting the critical role of altered Wnt and PI3K/Akt signaling in these behavioral domains of schizophrenia-related behaviors and proposing new avenues for therapeutic intervention.2026/09/11GSE307928GSM9234098GSM9234095GSM9234094GSM9234097GSM9234096GSM9234093GSM923409234290307928Mus musculus