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However, the mechanism by which microglia contribute to the disorder is unclear and recent data suggest that microglia do not play a causative role&lt;xref ref-type=\"bibr\" rid=\"bib67\"\/&gt;. Here, we use the retinogeniculate system to determine if and how microglia contribute to pathogenesis in a RTT mouse model, the Mecp2 null mouse (Mecp2tm1.1Bird\/y). We demonstrate that microglia contribute to pathogenesis by excessively engulfing, thereby eliminating, presynaptic inputs at end stages of disease (\u2265P56 Mecp2 null mice) concomitant with synapse loss. Furthermore, loss or gain of Mecp2 expression specifically in microglia (Cx3cr1CreER;Mecp2fl\/yor Cx3cr1CreER; Mecp2LSL\/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.<\/jats:p>","DOI":"10.7554\/elife.15224","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T10:48:20Z","timestamp":1468579700000},"source":"Crossref","is-referenced-by-count":142,"title":["Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression"],"prefix":"10.7554","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2201-6276","authenticated-orcid":true,"given":"Dorothy P","family":"Schafer","sequence":"first","affiliation":[{"name":"FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States"},{"name":"Department of Neurobiology, University of Massachusetts Medical School, Worcester, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T","family":"Heller","sequence":"additional","affiliation":[{"name":"FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States"},{"name":"Department of Neurobiology, University of Massachusetts Medical School, Worcester, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Gunner","sequence":"additional","affiliation":[{"name":"FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States"},{"name":"Department of Neurobiology, University of Massachusetts Medical School, Worcester, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Heller","sequence":"additional","affiliation":[{"name":"FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Gordon","sequence":"additional","affiliation":[{"name":"FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Hammond","sequence":"additional","affiliation":[{"name":"FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yochai","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Weizmann Institute of Science, Rehovot, 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