UMMS Affiliation
Department of Neurobiology; Schafer Lab
Publication Date
2016-07-26
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.
Keywords
Mecp2, Rett Syndrome, engulfment, microglia, mouse, neuroscience, synapse
Rights and Permissions
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
Source
Elife. 2016 Jul 26;5. pii: e15224. doi: 10.7554/eLife.15224. Link to article on publisher's site
Journal/Book/Conference Title
eLife
Related Resources
PubMed ID
27458802
Repository Citation
Schafer, Dorothy P.; Heller, Christopher T.; Gunner, Georgia; Heller, Molly; Gordon, Christopher; Hammond, Timothy; Wolf, Yochai; Jung, Steffen; and Stevens, Beth, "Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression" (2016). Open Access Articles. 2782.
https://escholarship.umassmed.edu/oapubs/2782
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.