FIGURE 3.

Bidirectionally dosage‐sensitive behavioral phenotypes are normalized with MECP2 transgene in male R294X mice. (A,B) Both male R294X and TG mice have decreased locomotor activity in the open field assay compared with WT littermates. Locomotor activity of male R294X TG mice is not different from WT littermates. (A) depicts distance traveled in centimeters across 5‐min bins. (B) quantifies total distance traveled across the 30‐min assay. (Colors as in Figure 1. Age: 20 weeks. WT n = 11; R294X n = 16; TG n = 16; R294X TG n = 16) (C) Male R294X mice have reduced motor coordination in the rotarod assay, while male TG mice have enhanced motor coordination, compared with WT littermates. Motor coordination in male R294X TG mice is not different from that of WT littermates, indicating normalization of phenotypes. (Age: 20 weeks. WT n = 12; R294X n = 16; TG n = 17; R294X TG n = 16) (D) Male R294X mice have decreased anxiety‐like behavior in the elevated zero maze assay, while male TG mice display increased anxiety‐like behavior, compared with WT littermates. Addition of MECP2 transgene normalizes anxiety‐like behavior in male R294X TG mice. (Age: 20 weeks. WT n = 12; R294X n = 16; TG n = 17; R294X TG n = 16) (E–G) During the training session of the fear conditioning assay (E), male TG mice display increased freezing after the first shock compared with WT mice, which is rescued in R294X TG mice. In the context (F) and cue (G) tests of the fear conditioning assay, male TG mice display increased freezing compared with WT littermates. Male R294X mice display decreased freezing relative to WT littermates in the cue test. Freezing levels of male R294X TG mice are not different from that of WT littermates. (Age: 22 weeks. WT n = 12; R294X n = 15; TG n = 17; R294X TG n = 16)