Figure 5. Defects in Behavioral Response to Novel Experience in MeCP2 S421A Knock-In Mice.

(A) Sociability is not affected by loss of MeCP2 S421 phosphorylation. Behavior of wild-type (n = 24) and MeCP2 S421A knock-in (n=21) mice in a three-chamber apparatus with a single novel mouse placed in a small wire cage on one of the side chambers. Data shown are time spent in each chamber over the 10 minute trial period. Wild-type and S421A mice spent significantly more time in the chamber with the novel mouse (WT p < 0.001, S421A p < 0.01). In this assay wild-type and MeCP2 S421A mice were statistically indistinguishable.

(B) MeCP2 S421A mice do not lose interest in familiar mice. Behavior of wild-type (n = 24) and MeCP2 S421A knock-in (n=21) mice in a three-chamber apparatus with a familiar mouse placed in one of the side chambers and a novel mouse placed in the opposite side chamber. Time spent in each chamber over the 10 minute trial period is shown. Wild-type mice spent significantly more time with the novel mouse than with the familiar mouse or alone (p < 0.01). The amount of time spend with each test mouse did not differ significantly for MeCP2 S421A knock-in mice.

(C) MeCP2 S421A mice do not distinguish between familiar and novel objects. Behavior of wild-type (n = 9) and MeCP2 S421A (n = 9) mice when placed in an arena with a familiar inanimate object and a novel inanimate object placed at opposite ends. In the short-term assay (i), the familiar object was first introduced 30 minutes prior to the trial. In the long-term assay (ii), the familiar object was first introduced 24 hours prior to the trial. Wild-type mice spend significantly more time interacting with the novel object than with the familiar object in both assays (i, p < 0.01; ii, p < 0.05), while MeCP2 S421A knock-in mice do not. Total time spent exploring each object over a 10 minute trial period is shown for each assay.

Data for all plots are mean ± SEM, p-values from one-way ANOVA with Bonferroni multiple comparison correction.