Fiber type grouping and advanced age‐related denervation of skeletal muscles from homozygous Sod1 knockout mice

Cu/Zn superoxide dismutase (SOD1) is an enzyme critically important for superoxide free radical elimination. Compared with age‐matched wild type littermates ( Sod1 +/+ ), ~2, ~10 and ~18 month old SOD1 homozygous knockout ( Sod1 −/− ) mice have smaller body and skeletal muscle masses. Following staining for succinate dehydrogenase, grouping of positive fibers were observed in muscles of Sod1 −/− mice from all three age groups. More advanced fiber type grouping was observed in skeletal muscles of 18 month old Sod1 −/− mice. While 2 month and 10 month old Sod1 +/+ mice did not display gross skeletal muscle structural abnormalities, 18 month old Sod1 −/− mice had extensive denervation of gastrocnemius muscle and some denervation of other hind limb muscles. The number of denervated muscle fibers observed in gastrocnemius muscles of 18 month old Sod1 −/− mice was comparable to that found in skeletal muscles of ~28 month old Sod1 +/+ mice. We conclude that lack of SOD1 enzymatic activity did not result in major muscle fiber structural abnormalities in skeletal muscles of young Sod1 −/− mice, but increased dramatically the onset and severity of age‐related denervation of skeletal muscles.