Recent large-scale studies in schizophrenia have identified two major biotypes through MRI analyses: one marked by basal ganglia and globus pallidus augmentation and another by neocortical volume reduction. Additionally, large-scale genomic studies have uncovered rare variants with substantial effect sizes. Based on these findings, we sought to replicate these biotypes in mice by combining rare variants with specific environmental factors. We also aim to explore the molecular, synaptic, and cellular foundations of each biotype. Notably, as the neocortical volume reduction subtype shows limited response to current drug therapies, modeling and analysis of this subtype may offer critical insights.