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© The Rockefeller University Press,
0021-9525/1999//531 $5.00
The Journal of Cell Biology, Volume 147, Number 3,
, 1999 531-544
Original Article |
Late Onset Death of Motor Neurons in Mice Overexpressing Wild-Type Peripherin
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
© 1999 The Rockefeller University Press
1.used in this paper: ALS, amyotrophic lateral sclerosis; DRG, dorsal root ganglion; IF, intermediate filament; IL-6, interleukin 6; LIF, leukemia inhibitory factor; NF, neurofilament; NF-H, neurofilament heavy subunit; NF-L, neurofilament light subunit; NF-M, neurofilament medium subunit; SOD1, copper/zinc superoxide dismutase; WT, wild-type
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