GSE113477
Activity-dependent aberrations in gene expression and alternative splicing in a mouse model of Rett syndrome
Rett syndrome (RTT) is a severe neurodevelopmental disorder that is caused by mutations in the gene methyl-CpG-binding-protein-2 (MECP2). However, the molecular mechanism by which these mutations mediate the RTT neuropathology remains enigmatic. In this study, we stimulated MeCP2-null cortical neurons (in vitro) and brains (in vivo) of a RTT mouse model to explore the effect of the loss of MeCP2 function on the activity-dependent transcriptomes of the cortex and hippocampus, respectively, using RNA-seq. These analyses revealed that the loss of MeCP2 results in aberrant global pattern of gene expression, characterized predominantly by higher levels of expression of activity-dependent genes, and anomalous alternative splicing events, specifically in response to neuronal activity. Overall design: For in vitro experiments, RNA-seq was performed on MeCP2-null (MT) and wild-type (WT) neuron-enriched cortical cultures that were either treated (T) with KCl for 3hr or not treated (N), after 10 days in culture. For in vivo experiments, RNA-seq was performed on hippocampi of MeCP2-null (MT) and wild-type (WT) mice that were either treated with kainic acid for 40 or 68 minutes, or not treated.