title: Rescue of behavioral and EEG deficits in male and female Mecp2-deficient mice by delayed Mecp2 gene reactivation.
abstract: Mutations of the X-linked gene encoding methyl CpG binding protein type 2 (MECP2) are the predominant cause of Rett syndrome, a severe neurodevelopmental condition that affects primarily females. Previous studies have shown that major phenotypic deficits arising from MeCP2-deficiency may be reversible, as the delayed reactivation of the Mecp2 gene in Mecp2-deficient mice improved aspects of their Rett-like phenotype. While encouraging for prospective gene replacement treatments, it remains unclear whether additional Rett syndrome co-morbidities recapitulated in Mecp2-deficient mice will be similarly responsive to the delayed reintroduction of functional Mecp2. Here, we show that the delayed reactivation of Mecp2 in both male and female Mecp2-deficient mice rescues established deficits in motor and anxiety-like behavior, epileptiform activity, cortical and hippocampal electroencephalogram patterning and thermoregulation. These findings indicate that neural circuitry deficits arising from the deficiency in Mecp2 are not engrained, and provide further evidence that delayed restoration of Mecp2 function can improve a wide spectrum of the Rett-like deficits recapitulated by Mecp2-deficient mice.
authors.affiliation: Division of Genetics and Development and.
authors.forename: Min
authors.initials: M
authors.lastname: Lang
authors.forename: Robert G
authors.initials: RG
authors.lastname: Wither
authors.forename: Sinisa
authors.initials: S
authors.lastname: Colic
authors.forename: Chiping
authors.initials: C
authors.lastname: Wu
authors.forename: Philippe P
authors.initials: PP
authors.lastname: Monnier
authors.forename: Berj L
authors.initials: BL
authors.lastname: Bardakjian
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: James H
authors.initials: JH
authors.lastname: Eubanks
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001833:Body Temperature Regulation; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009048:Motor Skills / Q000502:physiology; D010641:Phenotype; D015518:Rett Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D013629:Tamoxifen