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Updated: Jul 31, 2026
In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration
Published on: June 15, 2018
Late onset of motor neurons in mice overexpressing wild-type peripherin
J M Beaulieu1, M D Nguyen, J P Julien
1Centre for Research in Neurosciences, McGill University, The Montréal General Hsopital Research Institute, Montréal, Québec, H3G 1A4, Canada.
Abstract:
Peripherin, a type III intermediate filament (IF) protein, upregulated by injury and inflammatory cytokines, is a component of IF inclusion bodies associated with degenerating motor neurons in sporadic amyotrophic lateral sclerosis (ALS). We report here that sustained overexpression of wild-type peripherin in mice provokes massive and selective degeneration of motor axons during aging. Remarkably, the onset of peripherin-mediated disease was precipitated by a deficiency of neurofilament light (NF-L) protein, a phenomenon associated with sporadic ALS. In NF-L null mice, the overexpression of peripherin led to early- onset formation of IF inclusions and to the selective death of spinal motor neurons at 6 mo of age. We also report the formation of similar peripherin inclusions in presymptomatic transgenic mice expressing a mutant form of superoxide dismutase linked to ALS. Taken together, these results suggest that IF inclusions containing peripherin may play a contributory role in motor neuron disease.
Insights
Overexpressing peripherin protein in mice causes motor neuron degeneration. This neurodegeneration is accelerated by a lack of neurofilament light (NF-L) protein, suggesting a role in amyotrophic lateral sclerosis (ALS).
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Peripherin is a type III intermediate filament (IF) protein implicated in motor neuron degeneration.
- IF inclusion bodies containing peripherin are observed in sporadic amyotrophic lateral sclerosis (ALS).
Purpose of the Study:
- To investigate the role of peripherin overexpression in motor neuron degeneration.
- To determine if neurofilament light (NF-L) deficiency influences peripherin-mediated neurotoxicity.
Main Methods:
- Sustained overexpression of wild-type peripherin in mice.
- Utilized neurofilament light (NF-L) null mice.
- Examined IF inclusion formation and motor neuron survival.
Main Results:
- Peripherin overexpression alone caused age-dependent motor axon degeneration.
- NF-L deficiency precipitated early-onset IF inclusions and motor neuron death in peripherin-overexpressing mice.
- Similar peripherin inclusions were found in presymptomatic ALS-linked mutant SOD1 mice.
Conclusions:
- Peripherin overexpression can induce selective motor neuron degeneration.
- NF-L deficiency exacerbates peripherin-induced neurotoxicity, mimicking aspects of sporadic ALS.
- IF inclusions containing peripherin may contribute to motor neuron disease pathogenesis.
