Reference - Detail
| RRC ID | 46677 |
|---|---|
| Author | Speca DJ, Chihara D, Ashique AM, Bowers MS, Pierce-Shimomura JT, Lee J, Rabbee N, Speed TP, Gularte RJ, Chitwood J, Medrano JF, Liao M, Sonner JM, Eger EI 2nd, Peterson AS, McIntire SL. |
| Title | Conserved role of unc-79 in ethanol responses in lightweight mutant mice. |
| Journal | PLoS Genet |
| Abstract |
The mechanisms by which ethanol and inhaled anesthetics influence the nervous system are poorly understood. Here we describe the positional cloning and characterization of a new mouse mutation isolated in an N-ethyl-N-nitrosourea (ENU) forward mutagenesis screen for animals with enhanced locomotor activity. This allele, Lightweight (Lwt), disrupts the homolog of the Caenorhabditis elegans (C. elegans) unc-79 gene. While Lwt/Lwt homozygotes are perinatal lethal, Lightweight heterozygotes are dramatically hypersensitive to acute ethanol exposure. Experiments in C. elegans demonstrate a conserved hypersensitivity to ethanol in unc-79 mutants and extend this observation to the related unc-80 mutant and nca-1;nca-2 double mutants. Lightweight heterozygotes also exhibit an altered response to the anesthetic isoflurane, reminiscent of unc-79 invertebrate mutant phenotypes. Consistent with our initial mapping results, Lightweight heterozygotes are mildly hyperactive when exposed to a novel environment and are smaller than wild-type animals. In addition, Lightweight heterozygotes exhibit increased food consumption yet have a leaner body composition. Interestingly, Lightweight heterozygotes voluntarily consume more ethanol than wild-type littermates. The acute hypersensitivity to and increased voluntary consumption of ethanol observed in Lightweight heterozygous mice in combination with the observed hypersensitivity to ethanol in C. elegans unc-79, unc-80, and nca-1;nca-2 double mutants suggests a novel conserved pathway that might influence alcohol-related behaviors in humans. |
| Volume | 6(8) |
| Published | 2010-8-12 |
| DOI | 10.1371/journal.pgen.1001057 |
| PII | e1001057 |
| PMID | 20714347 |
| PMC | PMC2920847 |
| MeSH | Animals Body Weight* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Ethanol / metabolism* Female Ion Channels / genetics Ion Channels / metabolism Male Membrane Proteins Mice / genetics Mice / growth & development Mice / metabolism* Mice / physiology Mice, Inbred C57BL Motor Activity Mutation* Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism* |
| IF | 5.175 |
| Times Cited | 28 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | F1000Research |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1851 tm377 |