Abstract
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.
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