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dc.contributor.authorSpeca, DJ
dc.contributor.authorChihara, D
dc.contributor.authorAshique, AM
dc.contributor.authorBowers, MS
dc.contributor.authorPierce-Shimomura, JT
dc.contributor.authorLee, J
dc.contributor.authorRabbee, N
dc.contributor.authorSpeed, TP
dc.contributor.authorGularte, RJ
dc.contributor.authorChitwood, J
dc.contributor.authorMedrano, JF
dc.contributor.authorLiao, M
dc.contributor.authorSonner, JM
dc.contributor.authorEger, EI
dc.contributor.authorPeterson, AS
dc.contributor.authorMcIntire, SL
dc.date.accessioned2021-02-04T01:33:21Z
dc.date.available2021-02-04T01:33:21Z
dc.date.issued2010-08-01
dc.identifier.citationSpeca, 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). Conserved Role of unc-79 in Ethanol Responses in Lightweight Mutant Mice. PLOS GENETICS, 6 (8), https://doi.org/10.1371/journal.pgen.1001057.
dc.identifier.issn1553-7404
dc.identifier.urihttp://hdl.handle.net/11343/259400
dc.description.abstractThe 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.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.titleConserved Role of unc-79 in Ethanol Responses in Lightweight Mutant Mice
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pgen.1001057
melbourne.affiliation.departmentSchool of Mathematics and Statistics
melbourne.affiliation.facultyScience
melbourne.source.titlePLoS Genetics
melbourne.source.volume6
melbourne.source.issue8
dc.rights.licenseCC BY
melbourne.elementsid1212119
melbourne.contributor.authorSpeed, Terence
dc.identifier.eissn1553-7404
melbourne.accessrightsOpen Access


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