Reference - Detail
| RRC ID | 46585 |
|---|---|
| Author | Dimitriadi M, Sleigh JN, Walker A, Chang HC, Sen A, Kalloo G, Harris J, Barsby T, Walsh MB, Satterlee JS, Li C, Van Vactor D, Artavanis-Tsakonas S, Hart AC. |
| Title | Conserved genes act as modifiers of invertebrate SMN loss of function defects. |
| Journal | PLoS Genet |
| Abstract |
Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species. |
| Volume | 6(10) |
| Pages | e1001172 |
| Published | 2010-10-28 |
| DOI | 10.1371/journal.pgen.1001172 |
| PMID | 21124729 |
| PMC | PMC2965752 |
| MeSH | Analysis of Variance Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology Drosophila Proteins / genetics Drosophila Proteins / physiology Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Evolution, Molecular Female Genome, Helminth / genetics Genome, Insect / genetics Genome-Wide Association Study / methods* Humans Invertebrates / genetics* Invertebrates / growth & development Male Muscular Atrophy, Spinal / genetics Muscular Atrophy, Spinal / physiopathology Mutation Pupa / genetics Pupa / growth & development RNA Interference* SMN Complex Proteins / genetics* SMN Complex Proteins / physiology |
| IF | 5.175 |
| Times Cited | 68 |
| WOS Category | GENETICS & HEREDITY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm4255 tm604 |