Leukemia inhibitory factor ameliorates muscle fiber degeneration in the mdx mouse

Citation
L. Austin et al., Leukemia inhibitory factor ameliorates muscle fiber degeneration in the mdx mouse, MUSCLE NERV, 23(11), 2000, pp. 1700-1705
Citations number
13
Categorie Soggetti
da verificare
Journal title
MUSCLE & NERVE
ISSN journal
0148639X → ACNP
Volume
23
Issue
11
Year of publication
2000
Pages
1700 - 1705
Database
ISI
SICI code
0148-639X(200011)23:11<1700:LIFAMF>2.0.ZU;2-V
Abstract
Although the muscles of the mdx mouse lack dystrophin, the protein absent i n muscles of humans affected with Duchenne muscular dystrophy (DMD), the on ly 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 ex ogenously, 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 abdom inal 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 se ctions showed obvious muscle degeneration at 3 months of age in mdx mouse d iaphragms and further degeneration at 6 months in saline-perfused muscle. H emidiaphragm muscles continuously exposed to LIF over the same period conta ined more normal myofibers, larger regenerated fibers, and less adipose tis sue and other non-contractile tissue. Morphometric analysis of the diaphrag m sections was carried out. The LIF-treated animals showed a significant in crease in fiber number and size compared to saline rod controls. The amount of nonmuscle (connective tissue and adipose tissue) was significantly redu ced and the maximum force-producing capacity of isolated diaphragm muscle s trips was higher in LIF-treated mice. The results demonstrate that LIF trea tment ameliorates the dystrophic abnormalities in mdx mouse diaphragm. (C) 2000 John Wiley & Sons, Inc.