Fig. 1.

Sensory behavior and peripheral innervation are altered in MeCP2 KO rats. (A) Mechanical threshold (force in g) measured weekly between 30 and 51 d. Responses of the Mecp2^−/y (KO) rat were lower at all ages compared with WT rat (P < 0.001), becoming more pronounced at later ages (P < 0.001 genotype × strain interaction). WT showed increased threshold with age (P < 0.005 for 51 d vs. 30 and 37 d). (B) Mechanical sensitivity assessed as percent withdrawal to a normally subthreshold (6 g) stimulus. Responses of the KO rat were greater at all ages (P < 0.001), and became more pronounced at later ages (P < 0.001 genotype × strain interaction). WT response frequency remained constant, whereas KO responses were greater than 30 d at all other ages (P ≤ 0.005). (C) Cold plate temperature inducing a withdrawal response. The KO rat showed lower cold tolerance at all ages (P < 0.001) and remained constant throughout the testing period, whereas WT rats were more sensitive at 44 and 51 d relative to 30 d (P ≤ 0.01). (D) Noxious heat sensitivity defined as latency in seconds before a withdrawal response. KO rats were less sensitive to heat at all ages (P < 0.001). In A–D, significance was assessed by two-way repeated-measure ANOVA with post hoc comparisons using the Holm–Sidak method (n = 5 WT, 6 KO). (E) Immunostaining for PGP9.5 in footpad section of WT rat showing IENFs. (F) PGP9.5-ir IENFs in footpad section of KO rat. (Scale bar, 50 µm.) (G) IENF per unit length of the epidermis is greater in KO than in WT animals at both 30 and 51 d, with KO innervation increasing in this period. *P = 0.014 WT30 vs. KO30; P < 0.001, WT51 vs. KO51; P = 0.001, KO30 vs. KO51; P = 0.0153, WT30 vs. WT51. n at 30 d = 4 WT, 5 KO; n at 51 d = 8 WT, 9 KO. (H) PGP9.5 immunostaining in dorsal hairy skin epithelium in WT rat. (I) PGP9.5-ir in dorsal hairy skin epithelium of KO rat. (Scale bar, 50 µm.) (J) Quantitative comparison of PGP9.5-ir innervation density in dorsal hairy skin of WT and KO rats at 51 d (*P = 0.02; n = 5 WT, 6 KO).