MeCP2 S421A KI mice exhibit increased sensitivity to environmental stressors. a, MeCP2 KI mice and their WT littermates were injected with Veh 30 min before the tail-suspension test, and the amount of time immobile each minute of the 6 min test was recorded. b, MeCP2 KI mice and their WT littermates were injected with either Veh or imipramine (10 or 20 mg/kg) 30 min before the forced swim. Total time immobile and treading over the 6 min test was recorded. c, KI mice and WT littermates were tested for their preference for increasing concentrations of sucrose in a two-bottle choice test. n = 6–7 mice per group for a, n = 4–14 mice per group for b, and n = 7–10 mice per group for c. For a, *p < 0.05 compared with WT at each time point. For b, *p < 0.05 Veh compared with imipramine at 10 or 20 mg/kg within each genotype, and #p < 0.05 WT Veh compared with KI Veh.