GSE245024 Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [snRNA-Seq]

Contributors : Christopher P Tzeng ; Tess Whitwam ; Lisa D Boxer ; Michael E GreenbergSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusMutations in MECP2 give rise to Rett syndrome (RTT), an X-linked neurodevelop- mental disorder that results in broad cognitive impairments in females. While the exact etiology of RTT symptoms remains unknown, one possible explanation for its clinical presentation is that loss of MeCP2 causes miswiring of neural circuits due to defects in the brain ’s capacity to respond to changes in neuronal activity and sensory experience. Here, we show that MeCP2 is phosphorylated at four residues in the brain (S86, S274, T308, and S421) in response to neuronal activity, and we generate a quadruple knock-in (QKI) mouse line in which all four activity-dep endent sites are mutated to alanines to prevent phosphorylation. QKI mice do not display overt RTT phenotypes or detectable gene expression changes in two brain regions. However, electrophysiological recordings from the retinogeniculate synapse of QKI mice reveal that while synapse elimination is in itially normal at P14, it is significantly compromised at P20. Notably, this phenotype is distinct from the synapse refinement defect previously reported for Mecp2 null mice, where synapses initially refine but then regress after the third postnatal week. We thus propose a model in which activity-in duced phosphorylation of MeCP2 is critical for the proper timing of retin...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research