Perturbed cell fate decision by schizophrenia-associated AS3MT^d2d3 isoform during corticogenesis.

ABSTRACT: The neurodevelopmental theory of schizophrenia emphasizes early brain development in its etiology. Genome-wide association studies have linked schizophrenia to genetic variations of AS3MT (arsenite methyltransferase) gene, particularly the increased expression of AS3MT^d2d3 isoform. To investigate the biological basis of this association with schizophrenia pathophysiology, we established a transgenic mouse model (AS3MT^d2d3-Tg) ectopically expressing AS3MT^d2d3 at the cortical neural stem cells. AS3MT^d2d3-Tg mice exhibited enlarged ventricles and deficits in sensorimotor gating and sociability. Single-cell and single-nucleus RNA sequencing analyses of AS3MT^d2d3-Tg brains revealed cell fate imbalances and altered excitatory neuron c

SUBMITTER: Kim S 

PROVIDER: S-EPMC11952104 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature