CV neurons stimulate damaging responses from glia that then affect the neurons, that astrocytes are affected directly by a loss of MeCP2 and this is the primary source of neurotoxicity, or that both astrocytes and neurons are affected directly by a loss of MeCP2, but a loss of MeCP2 from glia causes a glial damage response that enhances the initial damage in neurons. The latter scenario has precedence in amyotrophic lateral sclerosis; although mutant SOD1 expression in motor neurons is required for disease initiation, neurotoxicity is also produced by damage in the neighboring mutant glia, which facilitates the initiation and progression of the disease44,45. Further in vivo studies are required to distinguish between these possible mechanisms. Toward this end, we are currently generating mouse models in which MeCP2-null astrocytes are produced in a background of wild-type neurons. Preliminary findings suggest that the selective loss of MeCP2 in astrocytes elicits, at least in part, an RTT-like phenotype neurons stimulate damaging responses from glia that then affect the neurons, that astrocytes are affected directly by a loss of MeCP2 and this is the primary source of neurotoxicity, or that both astrocytes and neurons are affected directly by a loss of MeCP2, but a loss of MeCP2 from glia causes a glial damage response that enhances the initial damage in neurons. The latter scenario has precedence in amyotrophic lateral sclerosis; although mutant SOD1 expression in motor neurons is required for disease initiation, neurotoxicity is also produced by damage in the neighboring mutant glia, which facilitates the initiation and progression of the disease44,45. Further in vivo studies are required to distinguish between these possible mechanisms. Toward this end, we are currently generating mouse models in which MeCP2-null astrocytes are produced in a background of wild-type neurons. Preliminary findings suggest that the selective loss of MeCP2 in astrocytes elicits, at least in part, an RTT-like phenotype