NMDAR is hypophosphorylated in NRG1(ΔTM)+/− and ErbB4+/− mutant mice, and hypophosphorylation is reversed by clozapine. A, NR2B Y1472 was hypophosphorylated in hippocampal lysates from NRG1(ΔTM)+/− and ErbB4+/− mutant mice (top, lanes 2 and 3, respectively) compared with age- and sex-matched wild-type (WT) C57BL/6 mice as shown by Western blot. Fyn/Src Y420 phosphorylation also was reduced in ErbB4+/− and NRG1(ΔTM)+/− mutant mice (bottom, lanes 2 and 3, respectively). Hippocampal lysates from Fyn−/− mice served as a control for NR2B Y1472 hypophosphorylation, as well as for Fyn/Src Y420 phosphorylation (fourth lane, top and bottom panels, respectively). Data are representative of five to six animals in at least three independent experiments; 25 μg of total protein was loaded per lane. B, Clozapine reverses NR2B hypophosphorylation in NRG1(ΔTM)+/− mice. NR2B Y1472 phosphorylation (top) was increased 2.5- to 3-fold in NRG1(ΔTM)+/− mice when normalized against total loading of NR2B (bottom). The same dose of clozapine had no effect on NR2B Y1472 phosphorylation (top) when administered to age- and sex-matched wild-type mice. Data representative of two to three animals in at least two independent experiments; 20 μg of total protein was loaded per lane.