Breathing disturbances in a model of Rett syndrome: A potential involvement of the glycine receptor α3 subunit?

The glycine receptor alpha 3 subunit is known to be a target for cAMP/PKA-mediated phosphorylation and regulation. Mice that lack this subunit are apparently normal but the 5-HT1A-receptor mediated modulation of respiratory network activity is disturbed. Since the intracellular cAMP-concentration is reduced in mice that lack the transcriptional modulator methyl-CpG-binding protein 2 (MeCP2) gene, we aimed to test if the alpha 3 subunit of the glycine receptor is involved in the development of the breathing phenotype of MeCP2-deficient mice (Mecp2(-/y)). Therefore, we generated a double knock-out mouse line that lacks both the Mecp2 gene as well as the gene (Glra3) for the alpha 3 subunit of the ionotropic glycine receptor. As compared to WT and Glra3(-/-) mice, both Mecp2(-/y) mice and Mecp2(-/y); Glra3(-/-) mice (DKO) showed a slower respiratory rate and a tendency towards higher numbers of apneas. Interestingly, the irregularity of the breathing was significantly reduced in DKO as compared to Mecp2(-/y) littermates. In the light of the unaltered survival of DKO mice, however, the contribution of the glycine receptor alpha 3 subunit for development and progression of the breathing disturbances in the mouse model of Rett syndrome appears to be only of minor relevance.