Nuclear changes in skeletal muscle extend to satellite cells in autosomal dominant Emery-Dreifuss muscular dystrophy/limb-girdle muscular dystrophy 1B

Young-Eun Park; Yukiko K Hayashi; Kanako Goto; Hirofumi Komaki; Yuichi Hayashi; Takashi Inuzuka; Satoru Noguchi; Ikuya Nonaka; Ichizo Nishino

doi:10.1016/j.nmd.2008.09.018

Nuclear changes in skeletal muscle extend to satellite cells in autosomal dominant Emery-Dreifuss muscular dystrophy/limb-girdle muscular dystrophy 1B

Neuromuscul Disord. 2009 Jan;19(1):29-36. doi: 10.1016/j.nmd.2008.09.018. Epub 2008 Dec 12.

Authors

Young-Eun Park¹, Yukiko K Hayashi, Kanako Goto, Hirofumi Komaki, Yuichi Hayashi, Takashi Inuzuka, Satoru Noguchi, Ikuya Nonaka, Ichizo Nishino

Affiliation

¹ Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, 187-8502 Tokyo, Japan.

PMID: 19070492
DOI: 10.1016/j.nmd.2008.09.018

Abstract

Autosomal forms of Emery-Dreifuss muscular dystrophy (AD-/AR-EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B) are caused by mutations in the gene encoding A-type lamins (LMNA). A-type lamins are major components of nuclear lamina and known to have important roles in maintaining nuclear integrity. LMNA mutations are also suggested to cause reduced myogenic differentiation potentials, implying that satellite cell nuclei in AD-EDMD/LGMD1B are likewise affected. We examined nuclear changes of skeletal muscles including satellite cells from four patients with AD-EDMD/LGMD1B by light and electron microscopy. We found that 92.5+/-5.0% of myonuclei had structural abnormalities, including shape irregularity and/or chromatin disorganization, and the presence of peri-/intranuclear vacuoles. Chromatin changes were also observed in 50% of the satellite cell nuclei. Increased number of Pax7-positive nuclei, but fewer number of MyoD-positive nuclei were seen on immunohistochemical analyses, suggesting functional alteration of satellite cells in addition to the nuclear morphological changes in AD-EDMD/LGMD1B.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Cell Nucleus / pathology*
Cell Nucleus / ultrastructure
Child
Child, Preschool
Chromatin / genetics
Chromatin / pathology
Chromosome Disorders / genetics
Chromosome Disorders / pathology
Chromosome Disorders / physiopathology
Female
Genes, Recessive / genetics
Humans
Immunohistochemistry
Lamin Type A / genetics
Microscopy, Electron
Middle Aged
Muscle, Skeletal / pathology*
Muscle, Skeletal / ultrastructure
Muscular Dystrophies, Limb-Girdle / genetics
Muscular Dystrophies, Limb-Girdle / pathology*
Muscular Dystrophies, Limb-Girdle / physiopathology
Muscular Dystrophy, Emery-Dreifuss / genetics
Muscular Dystrophy, Emery-Dreifuss / pathology*
Muscular Dystrophy, Emery-Dreifuss / physiopathology
Mutation / genetics
MyoD Protein / analysis
MyoD Protein / metabolism
PAX7 Transcription Factor / analysis
PAX7 Transcription Factor / metabolism
Satellite Cells, Skeletal Muscle / pathology*
Satellite Cells, Skeletal Muscle / ultrastructure
Vacuoles / pathology
Vacuoles / ultrastructure

Substances

Chromatin
LMNA protein, human
Lamin Type A
MyoD Protein
MyoD1 myogenic differentiation protein
PAX7 Transcription Factor
PAX7 protein, human