Rett syndrome (RTT) is a progressive neurological disorder primarily caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). The heterozygous female brain consists of mosaic of neurons containing both wild-type MeCP2 (MeCP2+) and mutant MeCP2 (MeCP2-). Three-dimensional morphological analysis was performed on individually genotyped layer V pyramidal neurons in the primary motor cortex of heterozygous (Mecp2(+/-) ) and wild-type (Mecp2(+/+) ) female mice ( > 6 mo.) from the Mecp2(tm1.1Jae) line. Comparing basal dendrite morphology, soma and nuclear size of MeCP2+ to MeCP2- neurons reveals a significant cell autonomous, genotype specific effect of Mecp2. MeCP2- neurons have 15% less total basal dendritic length, predominantly in the region 70-130 μm from the cell body and on average three fewer branch points, specifically loss in the second and third branch orders. Soma and nuclear areas of neurons of mice were analyzed across a range of ages (5-21 mo.) and X-chromosome inactivation (XCI) ratios (12-56%). On average, MeCP2- somata and nuclei were 15 and 13% smaller than MeCP2+ neurons respectively. In most respects branching morphology of neurons in wild-type brains (MeCP2 WT) was not distinguishable from MeCP2+ but somata and nuclei of MeCP2 WT neurons were larger than those of MeCP2+ neurons. These data reveal cell autonomous effects of Mecp2 mutation on dendritic morphology, but also suggest non-cell autonomous effects with respect to cell size. MeCP2+ and MeCP2- neuron sizes were not correlated with age, but were correlated with XCI ratio. Unexpectedly the MeCP2- neurons were smallest in brains where the XCI ratio was highly skewed toward MeCP2+, i.e., wild-type. This raises the possibility of cell non-autonomous effects that act through mechanisms other than globally secreted factors; perhaps competition for synaptic connections influences cell size and morphology in the genotypically mosaic brain of RTT model mice.
Pubmed ID: 25941473 RIS Download
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A software application which allows reconstruction of neuronal structures from confocal and multi-photon images. NeuronStudio provides tools for manual, semi-manual, and automatic tracing of the dendritic arbor, as well as manual and automatic detection and classification of dendritic spines. Advanced 2D and 3D visualization techniques facilitate the verification of the reconstruction, as well as allowing accurate manual editing. The most current version is Version 0.9.92 which was last updated on November 19, 2009.
View all literature mentionsProject portal dedicated to understand animal and machine intelligence and repository of data and tools. Suite of tools to analyze and graph imaging data. Image and data repository for large, publicly available neuro-specific data files and images. Contains tools for analytics, databases, cloud computing, and Web-services applied to both big neuroimages and big neurographs.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Mecp2tm1.1Jae/Mmucd from MMRRC.
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