Letter | Published:

The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy

Naturevolume 352pages536539 (1991) | Download Citation

Subjects

Abstract

ALTHOUGH murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin1,2, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD3–8. Here we show that the mdx mouse diaphragm exhibits a pattern of degeneration, fibrosis and severe functional deficit comparable to that of DMD limb muscle, although adult mice show no overt respiratory impairment. Progressive functional changes include reductions in strength (to 13.5% of control by two years of age), elasticity, twitch speed and fibre length. The collagen density rises to at least seven times that of control diaphragm and ten times that of mdx hind-limb muscle. By 1.5 years of age, similar but less severe histological changes emerge in the accessory muscles of respiration. On the basis of these findings, we propose that dystrophin deficiency alters the threshold for work-induced injury. Our data provide a quantitative framework for studying the pathogenesis of dystrophy and extend the application of the mdx mouse as an animal model.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Hoffman, E. P., Brown, R. H. & Kunkel, L. M. Cell 51, 919–928 (1987).

  2. 2

    Sicinski, P. et al. Science 244, 1578–1580 (1989).

  3. 3

    Dangain, J. & Vrbova, G. Muscle & Nerve 7, 700–704 (1984).

  4. 4

    Coulton, G. R., Curtin, N. A., Morgan, J. E. & Partridge, T. A. Neuropath. appl. Neurobiol. 14, 53–70 (1988).

  5. 5

    Coulton, G. R., Curtin, N. A., Morgan, J. E. & Partridge, T. A. Neuropath. appl. Neurobiol. 14, 299–314 (1988).

  6. 6

    Anderson, J. E., Bressler, B. H. & Ovalle, W. K. J. Muscle Res. Cell Motil. 9, 499–515 (1988).

  7. 7

    Mandel, J. L. Nature 339, 584–586 (1989).

  8. 8

    DiMario, J., Buffinger, N., Yamada, S. & Strohman, R. C. Science 244, 688–690 (1989).

  9. 9

    Switzer, B. R. & Summer, G. K. Analyt. Biochem. 39, 487–491 (1971).

  10. 10

    Narusawa, M. et al. J. Cell Biol. 104, 447–459 (1987).

  11. 11

    Webster, C., Silberstein, L., Hays, A. P. & Blau, H. M. Cell 52, 503–513 (1988).

  12. 12

    Kelly, A. M. Devl. Biol. 65, 1–10 (1978).

  13. 13

    Schmalbruch, H. & Hellhammer, U. Anat. Ftec. 189, 169–176 (1977).

  14. 14

    Dusterhoft, S., Yablonka-Reuveni, Z. & Pette, D. Differentiation 45, 185–191 (1990).

  15. 15

    Griffiths, R. I. J. Neurosci. Meth. 21, 159–165 (1987).

  16. 16

    Newman, S. et al. J. appl. Physiol. 56, 753–764 (1984).

  17. 17

    Smith, P. E. M. et al. New Engl. J. Med. 316, 1197–1204 (1987).

  18. 18

    Partridge, T. A., Morgan, J. E., Coulton, G. R., Hoffman, E. P. & Kunkel, L. M. Nature 337, 176–9 (1989).

  19. 19

    Wolff, J. A. et al. Science 247, 1465–1468 (1990).

  20. 20

    Lee, C. C., Pearlman, J. A., Chamberlain, J. S. & Caskey, C. T. Nature 349, 334–336 (1991).

  21. 21

    Menke, A. & Jockusch, H. Nature 349, 69–71 (1991).

  22. 22

    McCully, K. K. & Chance B., in Respiratory Muscles and Their Neuromotor Control 317–326 (Liss; New York, 1987).

  23. 23

    Kasper, C. E., White, T. P. & Maxwell, L. C. J. appl. Physiol. 68, 533–539 (1990).

  24. 24

    Stahl, W. R. J. appl. Physiol. 22, 453–460 (1967).

  25. 25

    Syme, D. A. J. Physiol. Lond. 424, 301–315 (1990).

Download references

Author information

Affiliations

  1. Schools of Medicine and Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, Pennsylvania, 19104, USA

    • H. H. Stedman
    • , H. L. Sweeney
    • , J. B. Shrager
    • , H. C. Maguire
    • , R. A. Panettieri
    • , B. Petrof
    • , M. Narusawa
    • , J. M. Leferovich
    • , J. T. Sladky
    •  & A. M. Kelly

Authors

  1. Search for H. H. Stedman in:

  2. Search for H. L. Sweeney in:

  3. Search for J. B. Shrager in:

  4. Search for H. C. Maguire in:

  5. Search for R. A. Panettieri in:

  6. Search for B. Petrof in:

  7. Search for M. Narusawa in:

  8. Search for J. M. Leferovich in:

  9. Search for J. T. Sladky in:

  10. Search for A. M. Kelly in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/352536a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.