RRC ID 46677
著者 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.
タイトル Conserved role of unc-79 in ethanol responses in lightweight mutant mice.
ジャーナル 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.
巻・号 6(8)
公開日 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
引用数 28
リソース情報
線虫 tm1851 tm377