Rescue of social interaction deficits in Shank3+ mutant mice. In the genotype/sex-matched social interaction test, Shank3 KO– mice displayed a significant reduction in social interaction time (A) compared with HET– mice. Shank3+ mice, including both genetic reversal transgenes, all displayed similar durations of social interaction (B) in the genotype/sex-matched social interaction test. In the social interaction with juvenile test of social memory, both HET and KO mice display deficits in social recognition (C). In the genetically reversed Shank3+ mice, however, all genotypes displayed similar levels of social memory (D). In the three-chamber test of sociability, Shank3– mice did not display a chamber preference in the initial trial (E). In second trial of this task, Shank3 HET– mice did not display a preference for the social target over the inanimate object (F). In the third trial of this task, neither Shank3 HET– nor KO– mice displayed a preference for social novelty (G). Shank3+ mice also did not display a baseline chamber preference in the initial trial of the three-chamber test (H). In the second trial, Shank3 HET+ mice did not display a preference for the social target over the inanimate object (I). In the third trial of this task, Shank3 HET+ mice did not display a preference for social novelty (J). Shank3– mice (K) along with Shank3+ mice (L) both display similar social interaction times, respectively, in approach of a novel, caged social target in the caged conspecific test. Data represented as mean ± SEM; *p < 0.05; **p < 0.01, ***p < 0.001, ****p < 0.0001; genotype sex match test n = 11 WT–, n = 8 HET–, n = 7 KO–; n = 11 WT+, n = 8 HET+, n = 7 KO+; all other behaviors n = 24 WT–, n = 16 HET–, n = 20 KO–, n = 24 WT+, n = 19 HET+, n = 16 KO+.