title: Advanced age-related denervation and fiber-type grouping in skeletal muscle of SOD1 knockout mice.
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.
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine–Northwest, Gary, IN 46409-1008, USA. tkostrom@iun.edu
authors.forename: Tatiana Y
authors.initials: TY
authors.lastname: Kostrominova
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D005260:Female; D008297:Male; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000172:deficiency*; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D008668:Metallothionein; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1