Studies on isolated human skeletal muscle fibers: Including a proposed pattern of nuclear distribution and a concept of nuclear territories

Abstract

Studies of human skeletal muscle fibers from tissue specimens isolated by supersonic cavitation, employing a Willens Polytron, show that the number of nuclei per millimeter, the surface area of fiber per nucleus, and the cytoplasmic volume per nucleus increase with fiber diameter, for fibers from the same muscle, from muscle to muscle, and from patient to patient. Skeletal muscle fibers from patients with Pompe's disease, muscular dystrophy (both autosomal and sex linked recessive juvenile forms), Riley-Day central autonomic dysfunction, and cardiomyopathy with skeletal muscle weakness show increased N/mm. and decreased A/N and V/N values, whereas fibers from patients with the Down syndrome show low N/mm. and high A/N and V/N values. Possibly abnormal fiber values were also observed in familial cerebellar atrophy with mental retardation, in 18 trisomy, Jansky-Bielschowsky disease, and ataxia-telangiectasia. Skeletal muscle fibers from autosomal recessive (“limb girdle”) muscular dystrophy show segmental, and those from Duchenne's dystrophy diffuse, hypernucleation. In Pompe's disease, acid mucopolysaccharide occurs in discrete “packages” in skeletal muscle, muscles of respiration showing less acid mucopolysaccharide than others. Evidence that the nuclei of skeletal muscle fibers are arranged in a pattern based on a hexagonal array, such that the fibers are covered by nuclear territories of relatively uniform size and shape, is presented, models of such architecture are presented, and possible biochemical implications of nuclear territories are discussed. Evidence that division of fiber nuclei is amitotic is presented. The concept that nuclear rows or chains in skeletal muscle fibers are nuclear clones is proposed, and possible biochemical implications of this arrangement are also discussed.