UMMS Affiliation

Department of Neurobiology; Schafer Lab

Publication Date

7-26-2016

Document Type

Article

Disciplines

Molecular and Cellular Neuroscience

Abstract

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.

Rights and Permissions

Citation: Elife. 2016 Jul 26;5. pii: e15224. doi: 10.7554/eLife.15224. Link to article on publisher's site

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.

DOI of Published Version

10.7554/eLife.15224

Related Resources

Link to Article in PubMed

Keywords

Mecp2, Rett Syndrome, engulfment, microglia, mouse, neuroscience, synapse

Journal/Book/Conference Title

eLife

PubMed ID

27458802

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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