males and females of c57bl/6-tg(ubc - gfp)30scha / j , c57bl/6j , b6.129p2(c)mecp2/j , b6.129p2-lyz2/j ( lysm ) , b6.129p2-mecp2/j , mecp2 , and c57bl/6j mice were purchased from jackson laboratories ( bar harbor , me ) ; b6.cg-mecp2 mice were a generous gift from dr .
andrew pieper , ( southwestern medical school , dallas , tx ) and were maintained in our lab on c57bl/6j background .
all procedures complied with regulations of the institutional animal care and use committee ( acuc ) at the university of virginia .
four week - old mice were subjected to lethal split - dose -irradiation ( 300 rad followed 48 hours later by 950 rad ) .
four hours after the second irradiation , mice were injected with 510 bone marrow cells .
after irradiation , mice were kept on drinking water fortified with sulfamethoxazole for two weeks in order to limit infection by opportunistic pathogens .
full methods and any associated references are available in the online version of the paper at www.nature.com/nature .
males and females of c57bl/6-tg(ubc - gfp)30scha / j , c57bl/6j , b6.129p2(c)mecp2/j , b6.129p2-lyz2/j ( lysm ) , b6.129p2-mecp2/j , mecp2 , and c57bl/6j mice were purchased from jackson laboratories ( bar harbor , me ) ; b6.cg-mecp2 mice were a generous gift from dr .
andrew pieper , ( southwestern medical school , dallas , tx ) and were maintained in our lab on c57bl/6j background .
all procedures complied with regulations of the institutional animal care and use committee ( acuc ) at the university of virginia .
four week - old mice were subjected to lethal split - dose -irradiation ( 300 rad followed 48 hours later by 950 rad ) .
four hours after the second irradiation , mice were injected with 510 bone marrow cells .
after irradiation , mice were kept on drinking water fortified with sulfamethoxazole for two weeks in order to limit infection by opportunistic pathogens .
full methods and any associated references are available in the online version of the paper at www.nature.com/nature .
 rett syndrome is an x - linked autism spectrum disorder . 
 the disease is characterized in the majority of cases by mutation of the mecp2 gene , which encodes a methyl - cpg - binding protein 15 . 
 although mecp2 is expressed in many tissues , the disease is generally attributed to a primary neuronal dysfunction 6 . however , as shown recently , glia , specifically astrocytes , also contribute to rett pathophysiology . 
 here we examined the role of another form of glia , microglia , in a murine model of rett syndrome . 
 transplantation of wild type bone marrow into irradiation - conditioned mecp2-null hosts resulted in engraftment of brain parenchyma by bone marrow - derived myeloid cells of microglial phenotype , and arrest of disease development . 
 however , when cranial irradiation was blocked by lead shield , and microglial engraftment was prevented , disease was not arrested . 
 similarly , targeted expression of mecp2 in myeloid cells , driven by lysmcre on an mecp2-null background , dramatically attenuated disease symptoms . thus , via multiple approaches , wild type mecp2-expressing microglia within the context of an mecp2-null male mouse arrested numerous facets of disease pathology ; lifespan was increased ; breathing patterns were normalized ; apneas were reduced ; body weight was increased to near wild type , and locomotor activity was improved . 
 mecp2+/ females also exhibited significant improvements as a result of wild type microglial engraftment . 
 these benefits mediated by wild type microglia , however , were diminished when phagocytic activity was inhibited pharmacologically using annexin v to block phosphatydilserine residues on apoptotic targets , thus preventing recognition and engulfment by tissue - resident phagocytes . 
 these results suggest the importance of microglial phagocytic activity in rett syndrome . 
 our data implicate microglia as major players in rett pathophysiology , and suggest that bone marrow transplantation might offer a feasible therapeutic approach for this devastating disorder . 