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

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15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1582-1593
Number of pages12
JournalFree Radical Biology and Medicine
Volume49
Issue number10
DOIs
StatePublished - Nov 30 2010

Keywords

  • Aging
  • Denervation
  • Fiber-type grouping
  • Free radicals
  • Skeletal muscle
  • Superoxide dismutase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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