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Elife DOI:10.7554/eLife.15224

Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression.

Publication TypeJournal Article
Year of Publication2016
AuthorsSchafer, DP, Heller, CT, Gunner, G, Heller, M, Gordon, C, Hammond, T, Wolf, Y, Jung, S, Stevens, B
JournalElife
Volume5
Date Published2016 Jul 26
ISSN2050-084X
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.

DOI10.7554/eLife.15224
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/27458802?dopt=Abstract

Alternate JournalElife
PubMed ID27458802
PubMed Central IDPMC4961457
Grant ListK99 MH102351 / MH / NIMH NIH HHS / United States
R00 MH102351 / MH / NIMH NIH HHS / United States
P30 HD018655 / HD / NICHD NIH HHS / United States
U54 HD090255 / HD / NICHD NIH HHS / United States
R01 NS071008 / NS / NINDS NIH HHS / United States