Reduced axonal diameter of peripheral nerve fibers in a mouse model of Rett syndrome

Neuroscience. 2017 Sep 1:358:261-268. doi: 10.1016/j.neuroscience.2017.06.061. Epub 2017 Jul 4.


Rett syndrome (RTT) is a neurological disorder characterized by motor and cognitive impairment, autonomic dysfunction and a loss of purposeful hand skills. In the majority of cases, typical RTT is caused by de novo mutations in the X-linked gene, MECP2. Alterations in the structure and function of neurons within the central nervous system of RTT patients and Mecp2-null mouse models are well established. In contrast, few studies have investigated the effects of MeCP2-deficiency on peripheral nerves. In this study, we conducted detailed morphometric as well as functional analysis of the sciatic nerves of symptomatic adult female Mecp2+/- mice. We observed a significant reduction in the mean diameter of myelinated nerve fibers in Mecp2+/- mice. In myelinated fibers, mitochondrial densities per unit area of axoplasm were significantly altered in Mecp2+/- mice. However, conduction properties of the sciatic nerve of Mecp2 knockout mice were not different from control. These subtle changes in myelinated peripheral nerve fibers in heterozygous Mecp2 knockout mice could potentially explain some RTT phenotypes.

Keywords: MECP2; Rett syndrome; mitochondria; sciatic nerve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / genetics
  • Animals
  • Axons / pathology*
  • Axons / ultrastructure
  • Biophysics
  • Disease Models, Animal
  • Electric Stimulation
  • Female
  • Methyl-CpG-Binding Protein 2 / genetics
  • Methyl-CpG-Binding Protein 2 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Mitochondria / pathology
  • Mitochondria / ultrastructure
  • Nerve Fibers, Myelinated / pathology*
  • Neural Conduction / genetics
  • Rett Syndrome / genetics
  • Rett Syndrome / pathology*
  • Sciatic Nerve / pathology*


  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2