Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans.
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 genet...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3861484?pdf=render |
| _version_ | 1818153243451064320 |
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| author | Martine Therrien Guy A Rouleau Patrick A Dion J Alex Parker |
| author_facet | Martine Therrien Guy A Rouleau Patrick A Dion J Alex Parker |
| author_sort | Martine Therrien |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T14:07:31Z |
| format | Article |
| id | doaj.art-af36c107a2a549d085f1e2395801d139 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T14:07:31Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-af36c107a2a549d085f1e2395801d1392022-12-22T01:03:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8345010.1371/journal.pone.0083450Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans.Martine TherrienGuy A RouleauPatrick A DionJ Alex ParkerAn 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.http://europepmc.org/articles/PMC3861484?pdf=render |
| spellingShingle | Martine Therrien Guy A Rouleau Patrick A Dion J Alex Parker Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans. PLoS ONE |
| title | Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans. |
| title_full | Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans. |
| title_fullStr | Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans. |
| title_full_unstemmed | Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans. |
| title_short | Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans. |
| title_sort | deletion of c9orf72 results in motor neuron degeneration and stress sensitivity in c elegans |
| url | http://europepmc.org/articles/PMC3861484?pdf=render |
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