title: Leukemia inhibitory factor ameliorates muscle fiber degeneration in the mdx mouse.
abstract: 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.
authors.affiliation: Melbourne Neuromuscular Research Institute, St. Vincent's Hospital, Victoria Parade, Fitzroy, Victoria 3065, Australia. austinl@svhm.org.au
authors.forename: L
authors.initials: L
authors.lastname: Austin
authors.forename: J J
authors.initials: JJ
authors.lastname: Bower
authors.forename: T M
authors.initials: TM
authors.lastname: Bennett
authors.forename: G S
authors.initials: GS
authors.lastname: Lynch
authors.forename: R
authors.initials: R
authors.lastname: Kapsa
authors.forename: J D
authors.initials: JD
authors.lastname: White
authors.forename: W
authors.initials: W
authors.lastname: Barnard
authors.forename: P
authors.initials: P
authors.lastname: Gregorevic
authors.forename: E
authors.initials: E
authors.lastname: Byrne
mesh_terms: D000818:Animals; D048429:Cell Size / Q000187:drug effects; D003964:Diaphragm / Q000166:cytology / Q000473:pathology / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology*; D015918:Infusion Pumps, Implantable; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011994:Recombinant Proteins