Late onset of motor neurons in mice overexpressing wild-type peripherin.
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.
Beaulieu
J M
JM
Centre for Research in Neurosciences, McGill University, The Montréal General Hsopital Research Institute, Montréal, Québec, H3G 1A4, Canada.
Nguyen
M D
MD
Julien
J P
JP
D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016923:Cell Death / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D064531:Peripherins; D015854:Up-Regulation
D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D064531:Peripherins