Hypersynchrony in a mouse model of Rett syndrome impairs ripple-dependent memory consolidation and leads to a decrease in experience-dependent refinement of place cell activities.
Label-free three-photon imaging of whole, uncleared intact organoids generated from Rett syndrome patients show shorter migration distances and slower migration speeds of mutant radially migrating neurons with more tortuous trajectories.
Laura Dean Heckman, Maria H Chahrour, Huda Y Zoghbi
Transgenic mice with Rett-causing mutations in MeCP2 reveal that a basic cluster in the C-terminus of the protein binds DNA and that both the methyl-CpG binding domain and the transcriptional repression domain are necessary to elicit toxicity in MECP2 duplication syndrome.
Dnmt3a regulates gene expression in inhibitory neurons by writing all mCH and some mCG, and MeCP2 reads some of these mCH sites driving a portion of these gene expression changes.
Genetically restoring Mecp2 expression only in GABAergic neurons in a mouse model of Rett syndrome improves inhibitory signaling, extends lifespan and rescues most but not all behavioral deficits.
Dorothy P Schafer, Christopher T Heller ... Beth Stevens
In mouse models of Rett Syndrome, global loss of the Mecp2 gene induces microglia to engulf excess synapses, while microglia-specific loss or gain of Mecp2 has little impact on disease.
Increased spontaneous calcium activity in Rett syndrome astrocytes is a key cell-autonomous phenotype that affects synaptic function and network activity.
Global brain transduction of the instability-prone Mecp2 transgene by systemic AAV-PHP.eB administration is safe and effective in protecting male and female Mecp2 mutant mice from the Rett syndrome disease phenotype.
A novel comparative genomics framework identifies MECP2 network proteins targeted by existing drugs, with three drugs validated in an in vitro Rett syndrome model.
