Normal myogenic cells from newborn mice restore normal histology to degenerating muscles of the mdx mouse.
Open Access
- 1 December 1990
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 111 (6), 2437-2449
- https://doi.org/10.1083/jcb.111.6.2437
Abstract
Dystrophin deficiency in skeletal muscle of the x-linked dystrophic (mdx) mouse can be partially remedied by implantation of normal muscle precursor cells (mpc) (Partridge, T. A., J. E. Morgan, G. R. Coulton, E. P. Hoffman, and L. M. Kunkel. 1989. Nature (Lond.). 337:176-179). However, it is difficult to determine whether this biochemical "rescue" results in any improvement in the structure or function of the treated muscle, because the vigorous regeneration of mdx muscle more than compensates for the degeneration (Coulton, G. R., N. A. Curtin, J. E. Morgan, and T. A. Partridge. 1988. Neuropathol. Appl. Neurobiol. 14:299-314). By using x-ray irradiation to prevent mpc proliferation, it is possible to study loss of mdx muscle fibers without the complicating effect of simultaneous fiber regeneration. Thus, improvements in fiber survival resulting from any potential therapy can be detected easily (Wakeford, S., D. J. Watt, and T. A. Patridge. 1990. Muscle & Nerve.) Here, we have implanted normal mpc, obtained from newborn mice, into such preirradiated mdx muscles, finding that it is far more extensively permeated and replaced by implanted mpc than is nonirradiated mdx muscle; this is evident both from analysis of glucose-6-phosphate isomerase isoenzyme markers and from immunoblots and immunostaining of dystrophin in the treated muscles. Incorporation of normal mpc markedly reduces the loss of muscle fibers and the deterioration of muscle structure which otherwise occurs in irradiated mdx muscles. Surprisingly, the regenerated fibers are largely peripherally nucleated, whereas regenerated mouse skeletal muscle fibers are normally centrally nucleated. We attribute this regeneration of apparently normal muscle to the tendency of newborn mouse mpc to recapitulate their neonatal ontogeny, even when grafted into 3-wk-old degenerating muscle.Keywords
This publication has 30 references indexed in Scilit:
- Dystrophin distribution in heterozygote mdx miceMuscle & Nerve, 1989
- Accumulation of collagen and altered fiber‐type ratios as indicators of abnormal muscle gene expression in the mdx dystrophic mouseMuscle & Nerve, 1989
- Conversion of mdx myofibres from dystrophin-negative to -positive by injection of normal myoblastsNature, 1989
- Characterization of Dystrophin in Muscle-Biopsy Specimens from Patients with Duchenne's or Becker's Muscular DystrophyNew England Journal of Medicine, 1988
- Expression of fast and slow isoforms of the Ca2+-ATPase in developing chick skeletal muscleDevelopmental Biology, 1987
- Electron microscopic and autoradiographic characterization of hindlimb muscle regeneration in the mdx mouseThe Anatomical Record, 1987
- Relationship of genotype and in vitro contractility in mdg/mdg ↔ +/+ “mosaic” myotubesMuscle & Nerve, 1984
- Differential response of satellite cells and embryonic myoblasts to a tumor promoterDevelopmental Biology, 1983
- The nuclear-cytoplasmic relationship in ‘mosaic‘ skeletal muscle fibers from mouse chimaerasExperimental Cell Research, 1983
- The contribution of exogenous cells to regenerating skeletal muscle : An isoenzyme study of muscle allografts in miceThe Journal of Pathology, 1980