Microtubule organisation in fibroblasts from dystrophic chickens and persons with Duchenne muscular dystrophy

Abstract

In spite of many attempts to correlate the expression of the Duchenne muscular dystrophy (DMD) genotype with defined phenotypic changes in both muscle and non-musde cells from affected individuals^1–4, the molecular basis of this X-linked genetic defect has not yet been identified. However, Shay and Fuseler reported recently⁵ that interphase cells derived from the muscle of newborn dystrophic chickens had greatly diminished cytoplasmic microtubule complexes, and they speculated that this might be due to a specific defect in the microtubule-organising centres. Insofar as microtubules are a major component of the intracellular cytoskeleton⁶, a network thought to interact with the cell-surface membrane⁷, the possibility that a microtubule defect might explain the membrane alterations associated with muscular dystrophies^1–4 makes this finding extremely interesting. To assess the generality of this finding with respect to chicken dystrophy and to extend the approach to DMD, we used indirect immunofluorescence with an antiserum to purified brain tubulin to examine the organisation of microtubules in cells from the muscle of dystrophic chickens and in skin fibroblasts from persons with DMD. Unlike Shay and Fuseler⁵, we find no lack of a microtubular network in cells derived from cardiac or skeletal muscle of chickens carrying the dystrophic gene (am). Furthermore, our examination of fibroblasts from persons with DMD revealed a similar extensive network of microtubules in each case.