Nuclear inclusions in innervated cultured muscle fibers from patients with oculopharyngeal muscular dystrophy.
We established monolayer muscle fiber cultures from muscle biopsies of 3 patients with oculopharyngeal muscular dystrophy (OPMD) who had characteristic intranuclear inclusions (INI-A) in their muscle fibers. Aneural cultures had normal morphology, except for a few muscle fibers that contained small vacuoles. Innervated cultures had large cytoplasmic vacuoles in a number of muscle fibers. Those muscle fibers were breaking easily, and could not be maintained longer than 2 months. Electron microscopy showed unusual intranuclear inclusions (INI-B) not previously reported in aneurally cultured muscle fibers of OPMD or in any normal or disease-control aneural or innervated cultured human muscle fibers. They resembled, but were not identical to, the INI-A, and they occurred in both the cultured fibers and the original muscle biopsies of all 3 patients. Our study demonstrate that (1) nuclear inclusions in OPMD reflect an intrinsic genetic defect; and (2) neuronal influence, advanced maturation, or both, seem to be essential for their induction in muscle fibers.
Tomé
F M
FM
Groupe de Recherche de Biologie et Pathologie Neuromusculaire, INSERM U 153, Paris, France.
Askanas
V
V
Engel
W K
WK
Alvarez
R B
RB
Lee
C S
CS
D000368:Aged; D001706:Biopsy; D002467:Cell Nucleus / Q000648:ultrastructure*; D002478:Cells, Cultured; D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000294:innervation / Q000473:pathology / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000473:pathology*; D009801:Oculomotor Muscles / Q000294:innervation / Q000473:pathology / Q000648:ultrastructure; D010609:Pharyngeal Muscles / Q000294:innervation / Q000473:pathology / Q000648:ultrastructure