Fig. 3: Social dysfunction of human neuronal chimeric mice exposed to Sev in early developmental stage.

a, b A three-chamber test on WT mice, WT mice treated with Sev at postnatal stage (postSev), control chimeric mice (chimera) and chimeric mice treated with Sev at the postnatal stage. c–e A resident–intruder assay on WT mice, WT mice treated with Sev at postnatal stage, control chimeric mice and chimeric mice treated with Sev at the postnatal stage. Notice the lower social preference and social interaction in chimeric mice treated with Sev at the postnatal stage. f, g A three-chamber test on control chimeric mice and chimeric mice made by Sev-pretreated hNPCs (preSev). h, i A resident–intruder assay on control chimeric mice and chimeric mice made by Sev-pretreated hNPCs. Notice the reduction of social preference scores and social interaction in chimeric mice made by Sev-pretreated hNPCs. j The experimental design for k–p. k, l Double immunostaining (k) and quantification (l) of GFP/DCX in chimeric mice derived from Sev-pretreated and hM3Dq-expressing hNPCs, which were treated with vehicle or CNO. CNO treatment significantly increased the migration of DCX/GFP-positive cells. m, n A three-chamber assay on chimeric mice derived from Sev-pretreated and hM3Dq-expressing hNPCs, which were treated with vehicle or CNO. o, p A resident–intruder assay on chimeric mice derived from Sev-pretreated and hM3Dq-expressing hNPCs, treated with vehicle or CNO. Notice the enhancement of social activity by CNO treatment. N = 6–9 mice per group. One-way ANOVA in b and e Student’s t-test in g, i, l, n, and p. *P < 0.05 and **P < 0.01. The error bars show s.e.m. Veh vehicle.