Fig. 1: Multiple global knockout models of ASD-associated genes exhibit tactile overreactivity in adulthood, with differences in ASD-associated behaviors.
a, Diagram showing tactile PPI of the startle reflex assay paradigm. The decrease in the startle response to a 120-dB acoustic pulse when preceded by a light air puff is defined as the effect of PPI (measured as a percentage). The interval between the prepulse and pulse was 250 ms; Stim, stimulus. b, Tactile PPI; n = 12 Gabrb3+/+ mice and n = 13 Gabrb3+/– mice, P = 0.0071; n = 14 Mecp2+/y mice and n = 5 Mecp2–/y mice, P = 0.0033; n = 14 Nlgn2+/+ mice and n = 18 Nlgn2+/– mice, P = 0.0043 for Nlgn2; n = 13 Rorb+/+ mice and n = 18 Rorbh1/+ mice, P = 0.0015. Data were analyzed by unpaired two-tailed t-tests. c, Response to the 0.9-psi air puff stimulus alone, expressed as a percentage of startle response to an acoustic startle stimulus; n = 12 Gabrb3+/+ mice and n = 13 Gabrb3+/– mice, P = 0.0071; n = 14 Mecp2+/y mice and n = 5 Mecp2–/y mice, P = 0.0033; n = 14 Nlgn2+/+ mice and n = 18 Nlgn2+/– mice, P = 0.0043 for Nlgn2; n = 13 Rorb+/+ mice and n = 18 Rorbh1/+ mice, P = 0.0457 for Gabrb3, P = 0.0003 for Mecp2, P = 0.0054 for Nlgn2 and P = 0.7374 for Rorb. Data were analyzed by two-tailed Mann–Whitney U-tests. d, Representative activity traces in the open field assay for mutant mice and control littermates. e, Fraction of time spent in the center of the open field chamber; n = 22 Gabrb3+/+ mice and n = 19 Gabrb3+/– mice, P < 0.0001; n = 15 Mecp2+/y mice and n = 8 Mecp2–/y mice, P = 0.0022; n = 23 Nlgn2+/+ mice and n = 30 Nlgn2+/– mice, P = 0.2050 for Nlgn2; n = 14 Rorb+/+ mice and n = 18 Rorbh1/+ mice, P = 0.5339. Data were analyzed by unpaired two-tailed t-tests. f, Representative heat maps showing time spent with a novel mouse or novel object (an empty cup) in the three-chamber social interaction assay for mutant mice and control littermates. g, Percent preference for a chamber containing a novel mouse versus a novel object in the three-chamber social interaction assay; n = 15 Gabrb3+/+ mice and n = 15 Gabrb3+/– mice, P = 0.0095; n = 9 Mecp2+/y mice and n = 8 Mecp2–/y mice, P = 0.0318; n = 10 Nlgn2+/+ mice and n = 14 Nlgn2+/– mice, P = 0.8603 for Nlgn2; n = 9 Rorb+/+ mice and n = 12 Rorbh1/+ mice, P = 0.9887. Data were analyzed by unpaired two-tailed t-tests. For b, c, e and g, data represent mean ± s.e.m. Statistical information is provided in Supplementary Table 1; NS, not significant; *P < 0.05; **P < 0.001; ***P < 0.0001.
