Multi-modal transcriptomic analysis reveals conserved and divergent molecular mechanisms underlying behaviors in mouse models of schizophrenia

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.