Original Article

Late Onset Death of Motor Neurons in Mice Overexpressing Wild-Type Peripherin

Correspondence to: Jean-Pierre Julien, The Montréal General Hospital Research Institute, 1650 Cedar Avenue, Montréal, Québec, H3G 1A4, Canada. Tel:(514) 934-8058 Fax:(514) 934-8265 E-mail:mdju{at}musica.mcgill.ca.

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.

Key Words: peripherin, neurofilament, ALS, motor neuron, transgenic

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