Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression
Authors
Schafer, Dorothy PHeller, Christopher T.
Gunner, Georgia
Heller, Molly
Gordon, Christopher
Hammond, Timothy
Wolf, Yochai
Jung, Steffen
Stevens, Beth
Document Type
Journal ArticlePublication Date
2016-07-26Keywords
Mecp2Rett Syndrome
engulfment
microglia
mouse
neuroscience
synapse
Molecular and Cellular Neuroscience
Metadata
Show full item recordAbstract
Microglia, the resident CNS macrophages, have been implicated in the pathogenesis of Rett Syndrome (RTT), an X-linked neurodevelopmental disorder. However, the mechanism by which microglia contribute to the disorder is unclear and recent data suggest that microglia do not play a causative role. Here, we use the retinogeniculate system to determine if and how microglia contribute to pathogenesis in a RTT mouse model, the Mecp2 null mouse (Mecp2(tm1.1Bird/y)). We demonstrate that microglia contribute to pathogenesis by excessively engulfing, thereby eliminating, presynaptic inputs at end stages of disease ( > /=P56 Mecp2 null mice) concomitant with synapse loss. Furthermore, loss or gain of Mecp2 expression specifically in microglia (Cx3cr1(CreER);Mecp2(fl/y)or Cx3cr1(Cr)(eER); Mecp2(LSL/y)) had little effect on excessive engulfment, synapse loss, or phenotypic abnormalities. Taken together, our data suggest that microglia contribute to end stages of disease by dismantling neural circuits rendered vulnerable by loss of Mecp2 in other CNS cell types.Source
Elife. 2016 Jul 26;5. pii: e15224. doi: 10.7554/eLife.15224. Link to article on publisher's site
DOI
10.7554/eLife.15224Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39973PubMed ID
27458802Related Resources
Rights
Copyright © 2016, Schafer et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.7554/eLife.15224
Scopus Count
Except where otherwise noted, this item's license is described as Copyright © 2016, Schafer et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.