Steven Mcintire

Publication Details

  • Conserved Role of unc-79 in Ethanol Responses in Lightweight Mutant Mice PLOS GENETICS Speca, D. J., Chihara, D., Ashique, A. M., Bowers, M. S., Pierce-Shimomura, J. T., Lee, J., Rabbee, N., Speed, T. P., Gularte, R. J., Chitwood, J., Medrano, J. F., Liao, M., Sonner, J. M., Eger, E. I., Peterson, A. S., McIntire, S. L. 2010; 6 (8)

    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.

    View details for DOI 10.1371/journal.pgen.1001057

    View details for Web of Science ID 000281383800013

    View details for PubMedID 20714347

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