Drosophila as a model for MECP2 gain of function in neurons.

PloS One
Fernando VonhoffCarsten Duch

Abstract

Methyl-CpG-binding protein 2 (MECP2) is a multi-functional regulator of gene expression. In humans loss of MECP2 function causes classic Rett syndrome, but gain of MECP2 function also causes mental retardation. Although mouse models provide valuable insight into Mecp2 gain and loss of function, the identification of MECP2 genetic targets and interactors remains time intensive and complicated. This study takes a step toward utilizing Drosophila as a model to identify genetic targets and cellular consequences of MECP2 gain-of function mutations in neurons, the principle cell type affected in patients with Rett-related mental retardation. We show that heterologous expression of human MECP2 in Drosophila motoneurons causes distinct defects in dendritic structure and motor behavior, as reported with MECP2 gain of function in humans and mice. Multiple lines of evidence suggest that these defects arise from specific MECP2 function. First, neurons with MECP2-induced dendrite loss show normal membrane currents. Second, dendritic phenotypes require an intact methyl-CpG-binding domain. Third, dendritic defects are amended by reducing the dose of the chromatin remodeling protein, osa, indicating that MECP2 may act via chromatin remodeling ...Continue Reading

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Citations

Dec 18, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Minghui JiangStelios M Smirnakis
Oct 17, 2012·Neuropharmacology·Zeynep Okray, Bassem A Hassan
Mar 27, 2016·Neurobiology of Disease·Alison A WilliamsCarsten Duch
Jul 22, 2016·PloS One·Alison A WilliamsCarsten Duch
Aug 5, 2016·Genes, Brain, and Behavior·T GuptaS J Certel
Jul 15, 2020·International Journal of Molecular Sciences·Taejoon KimIm-Soon Lee
Oct 12, 2014·Biology Open·David L Hess-HomeierSarah J Certel
Jun 3, 2021·International Journal of Molecular Sciences·Kirill SmirnovOlga Sysoeva

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Methods Mentioned

BETA
transgenic

Software Mentioned

AMIRA
Spike2
Excel
Statistica

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