Fast and slow strains of misfolded superoxide dismutase 1 in amyotrophic lateral sclerosis

Mutations in superoxide dismutase 1 (SOD1) account for ~10% of familial
amyotrophic lateral sclerosis (fALS) cases. Most SOD1 ALS cases show a 2-5
year clinical course, but a subset of patients exhibit a slowly
progressing illness lasting 10-20 years. Substantial evidence indicates
that disease-causing mutations in SOD1 promote misfolding and aggregation.
Spinal tissue homogenates from paralyzed transgenic mice containing
misfolded mutant SOD1 accelerate paralysis when injected into the spine or
sciatic nerve of young mutant SOD1 transgenic mice. Using this prion-like
seeding model in G85R-SOD1:YFP transgenic mice to initiate the disease
process, we show that human SOD1 variants associated with rapidly
progressing ALS produce SOD1-ALS strains that cause paralysis earlier than
mutations associated with slowly progressing disease. This data set
contains image data documenting pathological features of mice that became
paralyzed by seeding injections.