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Conserved role of unc-79 in ethanol responses in lightweight mutant mice
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نویسنده
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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.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 8
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چکیده
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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. © 2010 speca et al.
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آدرس
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department of neurology and the ernest gallo clinic and research center,university of california san francisco,emeryville,ca,united states,department of pharmacology,university of california davis,davis,ca, United States, department of neurology and the ernest gallo clinic and research center,university of california san francisco,emeryville,ca,united states,department of molecular biology,genentech,south san francisco,ca, United States, department of neurology and the ernest gallo clinic and research center,university of california san francisco,emeryville,ca,united states,department of psychiatry,virginia commonwealth university,richmond,va, United States, department of neurology and the ernest gallo clinic and research center,university of california san francisco,emeryville,ca,united states,college of natural sciences,section of neurobiology,university of texas,austin,tx, United States, department of neurology and the ernest gallo clinic and research center,university of california san francisco,emeryville,ca, United States, department of neurology and the ernest gallo clinic and research center,university of california san francisco,emeryville,ca, United States, department of statistics,university of california berkeley,berkeley,ca, United States, department of statistics,university of california berkeley,berkeley,ca,united states,bioinformatics division,walter and eliza hall institute of medical research,parkville, Australia, department of animal science,university of california davis,davis,ca, United States, department of animal science,university of california davis,davis,ca, United States, department of animal science,university of california davis,davis,ca, United States, department of anesthesia and perioperative care,university of california san francisco,san francisco,ca, United States, department of anesthesia and perioperative care,university of california san francisco,san francisco,ca, United States, department of anesthesia and perioperative care,university of california san francisco,san francisco,ca, United States, department of neurology and the ernest gallo clinic and research center,university of california san francisco,emeryville,ca,united states,department of molecular biology,genentech,south san francisco,ca, United States, department of neurology and the ernest gallo clinic and research center,university of california san francisco,emeryville,ca, United States
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Authors
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