• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of janatLink to Publisher's site
J Anat. Feb 1999; 194(Pt 2): 287–295.
PMCID: PMC1467923

The timing between skeletal muscle myoblast replication and fusion into myotubes, and the stability of regenerated dystrophic myofibres: an autoradiographic study in mdx mice

Abstract

In mdx mice, a model for Duchenne muscular dystrophy, the timing between the replication of myoblasts and their incorporation into myotubes was determined autoradiographically. Thirty-eight mdx mice aged 23 d were injected with tritiated thymidine to label myoblasts replicating early in the dystrophic process. At intervals from 8 h to 30 d after injection the tibialis anterior muscles were removed, processed for autoradiography and analysed for labelled central myonuclei (derived from the progeny of myoblasts which had been labelled at 23 d). At 8 h after injection there were no labelled central myonuclei, showing that the labelled myoblasts had not fused within this time. At 1 d, 2% of central myonuclei were labelled, at 2 d, up to 32% were labelled, at 3 d ~60% were labelled, and at 4 d the labelling peaked at 74%. In the 27 mice sampled from 5–30 d after injection, the levels of central myonuclear labelling varied enormously: from 1–63%. However, there was a consistent decrease in the numbers of labelled central myonuclei with time. This may have been due to dilution of the relative numbers of labelled myonuclei due to other, nonlabelled, myoblasts replicating after the availability of tritiated thymidine, and fusing. It was also possible that labelled myofibres underwent subsequent necrosis and were eliminated from the muscle. The proposal that a regenerated myofibre can undergo a subsequent cycle of necrosis and regeneration was supported by evidence of some necrotic myofibres with labelled and unlabelled central nuclei. These results have implications for understanding the cellular biology and pathology of dystrophic muscle, particularly in relation to myoblast transfer therapy as a potential treatment of Duchenne muscular dystrophy.

Keywords: Skeletal muscle, muscular dystrophy, myogenesis, muscle necrosis

Full Text

The Full Text of this article is available as a PDF (542K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Coulton GR, Curtin NA, Morgan JE, Partridge TA. The mdx mouse skeletal muscle myopathy: II. Contractile properties. Neuropathol Appl Neurobiol. 1988 Jul-Aug;14(4):299–314. [PubMed]
  • Coulton GR, Morgan JE, Partridge TA, Sloper JC. The mdx mouse skeletal muscle myopathy: I. A histological, morphometric and biochemical investigation. Neuropathol Appl Neurobiol. 1988 Jan-Feb;14(1):53–70. [PubMed]
  • Dilley R, McGeachie J. Block staining with p-phenylenediamine for light microscope autoradiography. J Histochem Cytochem. 1983 Aug;31(8):1015–1018. [PubMed]
  • Grounds MD. Commentary on the present state of knowledge for myoblast transfer therapy. Cell Transplant. 1996 May-Jun;5(3):431–433. [PubMed]
  • Grounds MD, McGeachie JK. A model of myogenesis in vivo, derived from detailed autoradiographic studies of regenerating skeletal muscle, challenges the concept of quantal mitosis. Cell Tissue Res. 1987 Dec;250(3):563–569. [PubMed]
  • Grounds MD, McGeachie JK. Myogenic cells of regenerating adult chicken muscle can fuse into myotubes after a single cell division in vivo. Exp Cell Res. 1989 Feb;180(2):429–439. [PubMed]
  • Grounds MD, McGeachie JK. Skeletal muscle regeneration after crush injury in dystrophic mdx mice: an autoradiographic study. Muscle Nerve. 1992 May;15(5):580–586. [PubMed]
  • Grounds MD, Yablonka-Reuveni Z. Molecular and cell biology of skeletal muscle regeneration. Mol Cell Biol Hum Dis Ser. 1993;3:210–256. [PubMed]
  • Karpati G, Carpenter S, Prescott S. Small-caliber skeletal muscle fibers do not suffer necrosis in mdx mouse dystrophy. Muscle Nerve. 1988 Aug;11(8):795–803. [PubMed]
  • McGeachie JK, Grounds MD. Initiation and duration of muscle precursor replication after mild and severe injury to skeletal muscle of mice. An autoradiographic study. Cell Tissue Res. 1987 Apr;248(1):125–130. [PubMed]
  • McGeachie JK, Grounds MD, Partridge TA, Morgan JE. Age-related changes in replication of myogenic cells in mdx mice: quantitative autoradiographic studies. J Neurol Sci. 1993 Nov;119(2):169–179. [PubMed]
  • McGeachie JK, Grounds MD. Retarded myogenic cell replication in regenerating skeletal muscles of old mice: an autoradiographic study in young and old BALBc and SJL/J mice. Cell Tissue Res. 1995 May;280(2):277–282. [PubMed]
  • Morgan JE. Cell and gene therapy in Duchenne muscular dystrophy. Hum Gene Ther. 1994 Feb;5(2):165–173. [PubMed]
  • Morgan JE, Hoffman EP, Partridge TA. Normal myogenic cells from newborn mice restore normal histology to degenerating muscles of the mdx mouse. J Cell Biol. 1990 Dec;111(6 Pt 1):2437–2449. [PMC free article] [PubMed]
  • Moss FP, Leblond CP. Nature of dividing nuclei in skeletal muscle of growing rats. J Cell Biol. 1970 Feb;44(2):459–462. [PMC free article] [PubMed]
  • Moss FP, Leblond CP. Satellite cells as the source of nuclei in muscles of growing rats. Anat Rec. 1971 Aug;170(4):421–435. [PubMed]
  • Robertson TA, Papadimitriou JM, Grounds MD. Fusion of myogenic cells to the newly sealed region of damaged myofibres in skeletal muscle regeneration. Neuropathol Appl Neurobiol. 1993 Aug;19(4):350–358. [PubMed]

Articles from Journal of Anatomy are provided here courtesy of Anatomical Society of Great Britain and Ireland

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...