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PMID:20714347

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Citation

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 and McIntire, SL (2010) Conserved role of unc-79 in ethanol responses in lightweight mutant mice. PLoS Genet. 6

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.

Links

PubMed PMC2920847 Online version:10.1371/journal.pgen.1001057

Keywords

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; Mice/genetics; Mice/growth & development; Mice/metabolism; Mice/physiology; Mice, Inbred C57BL; Motor Activity; Mutation; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:UNC79

acts_upstream_of_or_within

GO:0030534: adult behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3701691

P

Seeded From UniProt

complete

MOUSE:UNC79

acts_upstream_of_or_within

GO:0048149: behavioral response to ethanol

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3701691

P

Seeded From UniProt

complete

MOUSE:UNC79

acts_upstream_of_or_within

GO:0035264: multicellular organism growth

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3701691

P

Seeded From UniProt

complete


See also

References

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