Although the muscles of the mdx mouse lack dystrophin, the protein absent in muscles of humans affected with Duchenne muscular dystrophy (DMD), the only mdx muscle to degenerate in a manner similar to those of DMD boys is the diaphragm. We have previously shown that leukemia inhibitory factor (LIF) is a trauma factor that enhances muscle repair in vivo and, when applied exogenously, increases the fiber size of mdx skeletal muscle. Furthermore, we developed a controlled release device for LIF based on a calcium alginate rod (release rate about 0.5% per day). These rods were sutured to the abdominal surface of the hemidiaphragm of mdx mice 3 months old. At age 6 months the mice were killed and the diaphragm muscles fixed and sectioned. The sections showed obvious muscle degeneration at 3 months of age in mdx mouse diaphragms and further degeneration at 6 months in saline-perfused muscle. Hemidiaphragm muscles continuously exposed to LIF over the same period contained more normal myofibers, larger regenerated fibers, and less adipose tissue and other non-contractile tissue. Morphometric analysis of the diaphragm sections was carried out. The LIF-treated animals showed a significant increase in fiber number and size compared to saline rod controls. The amount of nonmuscle (connective tissue and adipose tissue) was significantly reduced and the maximum force-producing capacity of isolated diaphragm muscle strips was higher in LIF-treated mice. The results demonstrate that LIF treatment ameliorates the dystrophic abnormalities in mdx mouse diaphragm. (C) 2000 John Wiley and Sons, Inc.
|Number of pages||6|
|Journal||Muscle and Nerve|
|Early online date||23 Oct 2000|
|Publication status||Published - Nov 2000|
Austin, L., Bower, J. J., Bennett, T. M., Lynch, G. S., Kapsa, R., White, J. D., Barnard, W., Gregorevic, P., & Byrne, E. (2000). Leukemia inhibitory factor ameliorates muscle fiber degeneration in the mdx mouse. Muscle and Nerve, 23(11), 1700-1705. https://doi.org/10.1002/1097-4598(200011)23:11<1700::AID-MUS5>3.0.CO;2-W