Investigation of the epigenetic mechanism of swallowing and respiratory disturbances

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Rett syndrome (RTT) is caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). Mecp2-null mice exhibit frequent apnea similar to that seen in RTT, but epigenetic mechanisms underlying the respiratory disturbances are not well known. Because GABAergic neurotransmission has been reported to be impaired in the brain of Mecp2-null mice, we measured glutamate decarboxylase 1 (GAD1) mRNA expression in the respiratory nuclei in the medulla oblongata, and found that GAD1 mRNA was significantly reduced in Mecp2-null mice compared to wild-type mice at 2 weeks of age (p < 0.05). Methylation analysis of CpGs in the GAD1 proximal promoter revealed differences of the sites of methylated CpG between Mecp2-null mice and wild-type mice, and highly methylated CpGs in the GAD1 promoter of Mecp2-null mice.These results indicate that the altered GAD1 expression in the respiratory nuclei in the medulla may be responsible for the respiratory disturbances in Mecp2-null mice.