title: Nuclear changes in skeletal muscle extend to satellite cells in autosomal dominant Emery-Dreifuss muscular dystrophy/limb-girdle muscular dystrophy 1B.
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.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, 187-8502 Tokyo, Japan.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Park
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Kanako
authors.initials: K
authors.lastname: Goto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Komaki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Inuzuka
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: D002467:Cell Nucleus / Q000473:pathology* / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D002843:Chromatin / Q000235:genetics / Q000473:pathology; D025063:Chromosome Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D034904:Lamin Type A / Q000235:genetics; D008854:Microscopy, Electron; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology* / Q000648:ultrastructure; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D017570:MyoD Protein / Q000032:analysis / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000032:analysis / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology* / Q000648:ultrastructure; D014617:Vacuoles / Q000473:pathology / Q000648:ultrastructure
chemical_list: D002843:Chromatin; C494847:LMNA protein, human; D034904:Lamin Type A; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human