Format

Send to

Choose Destination
PLoS One. 2013 Dec 12;8(12):e83450. doi: 10.1371/journal.pone.0083450. eCollection 2013.

Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans.

Author information

1
Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada ; Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, Québec, Canada.
2
Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
3
Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, Québec, Canada ; Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
4
Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada ; Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, Québec, Canada ; Département de neuroscience, Université de Montréal, Montréal, Québec, Canada.

Abstract

An expansion of the hexanucleotide GGGGCC repeat in the first intron of C9ORF72 gene was recently linked to amyotrophic lateral sclerosis. It is not known if the mutation results in a gain of function, a loss of function or if, perhaps both mechanisms are linked to pathogenesis. We generated a genetic model of ALS to explore the biological consequences of a null mutation of the Caenorhabditis elegans C9ORF72 orthologue, F18A1.6, also called alfa-1. alfa-1 mutants displayed age-dependent motility defects leading to paralysis and the specific degeneration of GABAergic motor neurons. alfa-1 mutants showed differential susceptibility to environmental stress where osmotic stress provoked neurodegeneration. Finally, we observed that the motor defects caused by loss of alfa-1 were additive with the toxicity caused by mutant TDP-43 proteins, but not by the mutant FUS proteins. These data suggest that a loss of alfa-1/C9ORF72 expression may contribute to motor neuron degeneration in a pathway associated with other known ALS genes.

PMID:
24349511
PMCID:
PMC3861484
DOI:
10.1371/journal.pone.0083450
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center