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

ABSTRACT: 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 paralysed 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 paralysed G93A mice. A line of G93A mice that expresses at very low levels (VLE-G93A) was responsive to seeding but at low efficiency.

SUBMITTER: Xu G 

PROVIDER: S-EPMC12915820 | biostudies-literature | 2026 Dec

REPOSITORIES: biostudies-literature