imprint:
Proceedings of the National Academy of Sciences, 2018
Published in:Proceedings of the National Academy of Sciences
Language:
English
DOI:
10.1073/pnas.1722546115
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
<jats:title>Significance</jats:title>
<jats:p>
Rett syndrome (RTT) is a severe neurological disease affecting girls in their early childhood. The underlying cause of most RTT cases is mutations in the gene methyl-CpG-binding protein 2 (
<jats:italic>MECP2</jats:italic>
). How the loss of MeCP2 function in the brain due to these mutations causes such severe neurological symptoms remains a mystery. Here, we show widespread aberrations in gene expression and anomalous patterns of alternative splicing, specifically when neurons of RTT mice are stimulated. Furthermore, these aberrations occur in conjunction with higher seizure susceptibility in response to neuronal stimulation in these RTT mice. Our findings suggest that MeCP2 is required for adjusting the robust changes in gene transcription and for proper regulation of alternative splicing during neuronal stimulation.
</jats:p>