Neurodegeneration and early lethality in superoxide dismutase 2-deficient mice:
a comprehensive analysis of the central and peripheral nervous systems.
Authors Oh SS, Sullivan KA, Wilkinson JE, Backus C, Hayes JM, Sakowski SA, Feldman EL
Submitted By Eva Feldman on 8/1/2012
Status Published
Journal Neuroscience
Year 2012
Date Published 6/14/2012
Volume : Pages 212 : 201 - 213
PubMed Reference 22516022
Abstract The contribution of oxidative stress to diabetic complications including
neuropathy is widely known. Mitochondrial and cellular damage are associated
with the overproduction of reactive oxygen species and decreased levels or
function of the cellular antioxidant mitochondrial manganese superoxide
dismutase (SOD2). We hypothesized that targeted SOD2 deletion in the peripheral
nervous system using cre-lox technology under control of the nestin promoter
would accelerate neuropathy in a type 2 model of diabetes, the BKS.db/db mouse.
SOD2-deficient mice, however, demonstrated severe gait deformities and seizures
and died by 20 days of age. Examination of SOD2 expression levels revealed that
SOD2 was lost in brain and reduced in the spinal cord, but appeared normal in
dorsal root ganglia and peripheral nerves in SOD2-deficient mice. These findings
indicate incomplete targeted knockout of SOD2. Morphological examination
revealed cortical lesions similar to spongiform encephalopathy in the brain of
SOD2-deficient mice. No lesions were evident in the spinal cord, but changes in
myelin within the sciatic and sural nerves including a lack of cohesion between
layers of compact myelin were observed. Together, these results indicate that
targeted neuronal SOD2 knockout using the nestin promoter results in severe
central nervous system degeneration and perinatal lethality in mice. A specific
peripheral nervous system-targeting construct is required to examine the
consequences of SOD2 knockout in diabetic neuropathy.

Investigators with authorship
Eva FeldmanUniversity of Michigan