Behavioural and molecular characterisation of the Dlg2 haploinsufficiency rat model of genetic risk for psychiatric disorder
bioRxiv October 12, 2021 Sophie Waldron, Rachel Pass, Simonas Griesius et al.
Genetic evidence links disruptions in the DLG2 gene to increased risk for schizophrenia, autism, and intellectual disability. To explore psychiatric traits associated with reduced DLG2 function, a rat model with one functional copy of the Dlg2 gene (Dlg2+/-) was tested for anxiety, sensorimotor gating, reward responses, social behavior, and movement after phencyclidine administration. The rats showed reduced PSD-93 mRNA and protein without compensation from related genes. They exhibited an exaggerated locomotor response to phencyclidine, a hallmark of psychosis models, but no deficits in other behaviors. These findings suggest that DLG2 haploinsufficiency produces subtle, psychosis-related effects, unlike the more severe impairments seen in models with complete gene loss.