Figure 5. Loss of Mecp2 alters the molecular profile of the developing hippocampus.

(A) Given the premature loss of plasticity in Mecp2-null P8–11 mice, we examined gene expression differences at P10 and P18 in Mecp2-null compared with WT littermate control. Of the CA2-enriched genes (green font), Pcp4 and Spink8 were significantly lower in Mecp2-null compared with WT littermates (both unadjusted P value = 0.00730 and P = 0.0487, respectively). The CA2-enriched gene Fgf2 was significantly higher at both P10 (unadjusted P = 0.0101) and P18 (adjusted P = 0.0146). The inhibitory marker Gad1 was also significantly lower at P10 in Mecp2-null compared with WT (unadjusted P = 0.0332). Neither Rgs14 nor Acan (aggrecan) increased despite the increase in protein levels at P11 (Supplemental Figure 3A). We report no significant difference in the gene encoding PV (Parv), but note that the pattern of fold-change differences comparing Mecp2-null and WT depends on age. Genes with an adjusted P value less than 0.05 are designated with an asterisk, and genes with an unadjusted P value less than 0.05 are designated with “#”. Differences are presented as log₂ fold change compared with WT littermates. (B) The endogenous ECM-degrading enzyme matrix metalloproteinase 9 (MMP-9) is significantly decreased in a hippocampal lysate of Mecp2-null males compared with WT littermates (P45–60); ***P = 0.0005, unpaired 2-tailed t test (n = 6 for P37–42 for Mecp2-null males and for WT littermates). Right: MMP-9 band intensity from Mecp2-null males was normalized to β-actin band intensity and divided by the average of the values from WT littermates. See complete unedited blots in the supplemental material.