AUTHOR=Hülsmann Swen , Mesuret Guillaume , Dannenberg Julia , Arnoldt Mauricio , Niebert Marcus 

TITLE=GlyT2-Dependent Preservation of MECP2-Expression in Inhibitory Neurons Improves Early Respiratory Symptoms but Does Not Rescue Survival in a Mouse Model of Rett Syndrome

JOURNAL=Frontiers in Physiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2016.00385

DOI=10.3389/fphys.2016.00385

ISSN=1664-042X

ABSTRACT=<p>Mutations in methyl-CpG-binding protein 2 (MECP2) gene have been shown to manifest in a neurodevelopmental disorder that is called Rett syndrome. A typical problem that occurs during development is a disturbance of breathing. To address the role of inhibitory neurons, we generated a mouse line that restores MECP2 in inhibitory neurons in the brainstem by crossbreeding a mouse line that expresses the Cre-recombinase (Cre) in inhibitory neurons under the control of the glycine transporter 2 (<italic>GlyT2, slc6a5</italic>) promotor (<italic>GlyT2</italic>-Cre) with a mouse line that has a floxed-stop mutation of the <italic>Mecp2</italic> gene (<italic>Mecp2</italic><sup>stop/y</sup>). Unrestrained whole-body-plethysmography at postnatal day P60 revealed a low respiratory rate and prolonged respiratory pauses in <italic>Mecp2</italic><sup>stop/y</sup> mice. In contrast, <italic>GlyT2</italic>-Cre positive <italic>Mecp2</italic><sup>stop/y</sup> mice (Cre<sup>+</sup><italic>; Mecp2</italic><sup>stop/y</sup>) showed greatly improved respiration and were indistinguishable from wild type littermates. These data support the concept that alterations in inhibitory neurons are important for the development of the respiratory phenotype in Rett syndrome.</p>