title: A mouse model for MeCP2 duplication syndrome: MeCP2 overexpression impairs learning and memory and synaptic transmission.
abstract: Rett syndrome and MECP2 duplication syndrome are neurodevelopmental disorders that arise from loss-of-function and gain-of-function alterations in methyl-CpG binding protein 2 (MeCP2) expression, respectively. Although there have been studies examining MeCP2 loss of function in animal models, there is limited information on MeCP2 overexpression in animal models. Here, we characterize a mouse line with MeCP2 overexpression restricted to neurons (Tau-Mecp2). This MeCP2 overexpression line shows motor coordination deficits, heightened anxiety, and impairments in learning and memory that are accompanied by deficits in long-term potentiation and short-term synaptic plasticity. Whole-cell voltage-clamp recordings of cultured hippocampal neurons from Tau-Mecp2 mice reveal augmented frequency of miniature EPSCs with no change in miniature IPSCs, indicating that overexpression of MeCP2 selectively impacts excitatory synapse function. Moreover, we show that alterations in transcriptional repression mechanisms underlie the synaptic phenotypes in hippocampal neurons from the Tau-Mecp2 mice. These results demonstrate that the Tau-Mecp2 mouse line recapitulates many key phenotypes of MECP2 duplication syndrome and support the use of these mice to further study this devastating disorder.
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
authors.forename: Elisa S
authors.initials: ES
authors.lastname: Na
authors.forename: Erika D
authors.initials: ED
authors.lastname: Nelson
authors.forename: Megumi
authors.initials: M
authors.lastname: Adachi
authors.forename: Anita E
authors.initials: AE
authors.lastname: Autry
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Mahgoub
authors.forename: Ege T
authors.initials: ET
authors.lastname: Kavalali
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Monteggia
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020440:Gene Duplication / Q000502:physiology*; D005786:Gene Expression Regulation; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D051783:Methyl-CpG-Binding Protein 2 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D013577:Syndrome; D016875:tau Proteins / Q000235:genetics
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D016875:tau Proteins