Nuclear inclusions in innervated cultured muscle fibers from patients with oculopharyngeal muscular dystrophy

Abstract

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 them 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 demonstrates 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.