Data from: Efficient induction of motor neuron disease in transgenic G93A SOD1 mice by prion-like seeding

Mutations in superoxide dismutase 1 (SOD1) cause paralysis in familial
amyotrophic lateral sclerosis and promote its misfolding into neurotoxic
aggregates. Previous studies have shown that mice expressing the
ALS-causing G85R variant of SOD1 develop paralysis much faster after
intraspinal injection of spinal homogenates from paralyzed G85R SOD1 mice.
These findings, and other studies in cell models, established the prionoid
templating properties of misfolded mutant SOD1. Previously, however, we
noted that the widely used Gur1-G93A SOD1 mice, which express at high
levels and develop paralysis by 6 months of age, were resistant to seeding
by homogenates from paralyzed G93A mice. A line of G93A mice that express
at very low levels (VLE-G93A) were responsive to seeding but at low
efficiency. The poor susceptibility of G93A-SOD1 mice to seeding was not
what we expected if prion-like propagation is essential to SOD1 ALS
pathogenesis. In our prior, studies seeding homogenates from paralyzed
G93A-SOD1 mice were injected into the spine of newborn mice, leading us to
question whether older G93A SOD1 mice might be more susceptible to
seeding. Here, we establish that adult VLE G93A SOD1 mice (up to 12 months
of age) injected intrathecally with seeding homogenates containing
misfolded G93A or G85R SOD1 developed accelerated motor neuron disease
efficiently. Thus, we demonstrate that both the route and age of
inoculation can influence the efficiency of SOD1 seeding to induce motor
neuron disease in VLE G93A-SOD1 mice. These data, together with our
earlier reports, suggest that prion-like templating contributes to disease
progression in SOD1-ALS.