Developmental loss of MeCP2 from VIP interneurons impairs cortical function and behavior
- Yale University, United States
Abstract
Rett Syndrome is a devastating neurodevelopmental disorder resulting from mutations in the gene MECP2. Mutations of Mecp2 restricted to GABAergic cell types largely replicate the behavioral phenotypes associated with mouse models of Rett Syndrome, suggesting a pathophysiological role for inhibitory interneurons. Recent work has suggested that vasoactive intestinal peptide-expressing (VIP) interneurons may play a critical role in the proper development and function of cortical circuits, making them a potentially key point of vulnerability in neurodevelopmental disorders. However, little is known about the role of VIP interneurons in Rett Syndrome. Here we find that loss of MeCP2 specifically from VIP interneurons replicates key neural and behavioral phenotypes observed following global Mecp2 loss of function.
Data availability
Source data files are included for each figure and supplemental figure. Analysis code is available at https://github.com/jesscardin/Miri-Vinck-et-al. All data included in this study will be freely available upon request, as the data files and associated intermediate analysis files are very large (400GB) and depositing the full data is not feasible.
Article and author information
Author details
Funding
Simons Foundation (SFARI)
- Jessica A Cardin
National Institute of Mental Health (MH113852)
- Jessica A Cardin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were approved by the Institutional Animal Care and Use Committee of Yale University (#11317).
Copyright
© 2020, Mossner et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Developmental loss of MeCP2 from VIP interneurons impairs cortical function and behavior
eLife 9:e55639.
https://doi.org/10.7554/eLife.55639
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