Normal myogenic cells from newborn mice restore normal histology to degenerating muscles of the mdx mouse

Journal Article · Sat Dec 01 04:00:00 EST 1990 · Journal of Cell Biology; (USA)

DOI:https://doi.org/10.1083/jcb.111.6.2437· OSTI ID:6140554

Morgan, J E; Hoffman, E P; Partridge, T A ^[1]

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1. Charing Cross and Westminster Medical School, London (England)

Dystrophin deficiency in skeletal muscle of the x-linked dystrophic (mdx) mouse can be partially remedied by implantation of normal muscle precursor cells (mpc). 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. 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. 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.

• OSTI ID: 6140554
• Journal Information: Journal of Cell Biology; (USA), Journal Name: Journal of Cell Biology; (USA) Vol. 111:6 Pt 1; ISSN 0021-9525; ISSN JCLBA
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL MARKERS
BIOLOGICAL RECOVERY
BIOLOGICAL REGENERATION
CELL PROLIFERATION
ELECTROMAGNETIC RADIATION
ENZYMES
IMPLANTS
INHIBITION
IONIZING RADIATIONS
ISOMERASES
MAMMALS
MICE
MUSCLES
NEONATES
PATHOLOGICAL CHANGES
RADIATIONS
RECOVERY
RODENTS
VERTEBRATES
X RADIATION