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Wild-type microglia do not reverse pathology in mouse models of Rett syndrome

2015; Nature Portfolio; Volume: 521; Issue: 7552 Linguagem: Inglês

10.1038/nature14444

1476-4687

Jieqi Wang, Eike Wegener, Teng-Wei Huang, Smitha Sripathy, Hector De Jesús‐Cortés, Pin Xu, Stephanie Tran, Whitney Knobbe, Vid Leko, Jeremiah K. Britt, Ruth Starwalt, Latisha McDaniel, Chris S. Ward, Diana Parra, Benjamin Newcomb, Uyen Lao, Cynthia Nourigat, David Flowers, Sean M. Cullen, Nikolas L. Jorstad, Yue Yang, Lena Glaskova, Sébastien Vingeau, Sébastien Vigneau, Julia Kozlitina, Michael J. Yetman, Joanna L. Jankowsky, Sybille D. Reichardt, Holger M. Reichardt, Jutta Gärtner, Marisa S. Bartolomei, Min Fang, Keith Loeb, C. Dirk Keene, Irwin Bernstein, Margaret A. Goodell, Daniel J Brat, Peter Huppke, Jeffrey L. Neul, Antonio Bedalov, Andrew A. Pieper,

RNA modifications and cancer

arising from N. C. Derecki et al. , 105–109 (2012); doi:10.1038/nature10907 Rett syndrome is a severe neurodevelopmental disorder caused by mutations in the X chromosomal gene MECP2 (ref. 1), and its treatment so far is symptomatic. Mecp2 disruption in mice phenocopies major features of the syndrome2 that can be reversed after Mecp2 re-expression3. Recently, Derecki et al.4 reported that transplantation of wild-type bone marrow into lethally irradiated Mecp2-null (Mecp2tm1.1Jae/y) mice prevented neurological decline and early death by restoring microglial phagocytic activity against apoptotic targets4, and clinical trials of bone marrow transplantation (BMT) for patients with Rett syndrome have thus been initiated5. We aimed to replicate and extend the BMT experiments in three different Rett syndrome mouse models, but found that despite robust microglial engraftment, BMT from wild-type donors did not prevent early death or ameliorate neurological deficits. Furthermore, early and specific Mecp2 genetic expression in microglia did not rescue Mecp2-deficient mice.