Mutations in the transcription factor methyl-CpG-binding-protein 2 (MeCP2) cause 
a delayed-onset neurodevelopmental disorder known as Rett syndrome (RTT). 
Although alteration in serotonin levels have been reported in RTT patients, the 
molecular mechanisms underlying these defects are not well understood. 
Therefore, we chose to investigate the serotonergic system in hippocampus and 
brainstem of male Mecp2-/y knock-out mice in the B6.129P2(C)-Mecp2(tm1.1Bird) 
mouse model of RTT. The serotonergic system in mouse is comprised of 16 genes, 
whose mRNA expression profile was analyzed by quantitative RT-PCR. Mecp2-/y mice 
are an established animal model for RTT displaying most of the cognitive and 
physical impairments of human patients and the selected areas receive 
significant modulation through serotonin. Using anatomically and functional 
characterized areas, we found region-specific differential expression between 
wild type and Mecp2-/y mice at post-natal day 40. In brainstem, we found five 
genes to be dysregulated, while in hippocampus, two genes were dysregulated. The 
one gene dysregulated in both brain regions was dopamine decarboxylase, but of 
special interest is the serotonin receptor 5b (5-ht5b), which showed 75-fold 
dysregulation in brainstem of Mecp2-/y mice. This dysregulation was not due to 
upregulation, but due to failure of down-regulation in Mecp2-/y mice during 
development. Detailed analysis of 5-ht5b revealed a receptor that localizes to 
endosomes and interacts with Gαi proteins.