Details

Autor(en) / Beteiligte

• Therrien, Martine
• Rouleau, Guy A
• Dion, Patrick A
• Parker, J Alex
• Dupuy, Denis

Titel

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

Ist Teil von

• PloS one, 2013-12, Vol.8 (12), p.e83450

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.