arising from N. C. Derecki et al.Nature484, 105–109 (2012); doi:10.1038/nature10907

Rett syndrome is a severe neurodevelopmental disorder caused by mutations in the X chromosomal gene MECP2 (ref. ), and its treatment so far is symptomatic. Mecp2 disruption in mice phenocopies major features of the syndrome that can be reversed after Mecp2 re-expression. Recently, Derecki et al. reported that transplantation of wild-type bone marrow into lethally irradiated Mecp2-null (Mecp2^tm1.1Jae/y) mice prevented neurological decline and early death by restoring microglial phagocytic activity against apoptotic targets, and clinical trials of bone marrow transplantation (BMT) for patients with Rett syndrome have thus been initiated. 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.