Developmentally dynamic, non-convergent transcriptomic profiles in CNV models for schizophrenia risk

Although numerous rare copy number variations (CNVs) with high risk for schizophrenia have been identified, they show no obvious overlap in gene content or function. We hypothesized that the downstream effects of schizophrenia-associated CNVs converge on shared molecular pathways.

To test this, we profiled the prefrontal cortex of five schizophrenia-associated CNV mouse models—15q13.3del, 3q29del, 1q21.1del, 22q11.2del, and 16p11.2dup—using single-cell RNA sequencing across two developmental stages: adolescence and adulthood. From 292,943 high-quality single-cell transcriptomes, we identified distinct age- and cell type-specific patterns of differential gene expression and biological pathway perturbations in each model.