Advanced age-related denervation and fiber-type grouping in skeletal muscle of SOD1 knockout mice

In this study skeletal muscles from 1.5- and 10-month-old Cu/Zn superoxide dismutase (SOD1) homozygous knockout (JLSod1−/−) mice obtained from The Jackson Laboratory (C57Bl6/129SvEv background) were compared with muscles from age- and sex-matched heterozygous (JLSod1+/−) littermates. The results of this study were compared with previously published data on two different strains of Sod1−/− mice: one from Dr. Epstein's laboratory (ELSod1−/−; C57Bl6 background) and the other from Cephalon, Inc. (CSod1−/−; 129/CD-1 background). Grouping of succinate dehydrogenase-positive fibers characterized muscles of Sod1−/− mice from all three strains. The 10-month-old Sod1−/−C and JL mice displayed pronounced denervation of the gastrocnemius muscle, whereas the ELSod1−/− mice displayed a small degree of denervation at this age, but developed accelerated age-related denervation later on. Denervation markers were up-regulated in skeletal muscle of 10-month-old JLSod1−/− mice. This study is the first to show that metallothionein mRNA and protein expression was up-regulated in the skeletal muscle of 10-month-old JLSod1−/− mice and was mostly localized to the small atrophic muscle fibers. In conclusion, all three strains of Sod1−/− mice develop accelerated age-related muscle denervation, but the genetic background has significant influence on the progress of denervation.