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Lmo genes regulate behavioral responses to ethanol in Drosophila melanogaster and the mouse.
Alcohol Clin Exp Res 2011; 35(9):1600-6AC

Abstract

BACKGROUND

Previous work from our laboratory demonstrated a role for the Drosophila Lim-only (dLmo) gene in regulating behavioral responses to cocaine. Herein, we examined whether dLmo influences the flies' sensitivity to ethanol's sedating effects. We also investigated whether 1 of the mammalian homologs of dLmo, Lmo3, is involved in behavioral responses to ethanol in mice.

METHODS

To examine dLmo function in ethanol-induced sedation, mutant flies with reduced or increased dLmo expression were tested using the loss of righting (LOR) assay. To determine whether mouse Lmo3 regulates behavioral responses to ethanol, we generated transgenic mice expressing a short-hairpin RNA targeting Lmo3 for RNA interference-mediated knockdown by lentiviral infection of single cell embryos. Adult founder mice, expressing varying amounts of Lmo3 in the brain, were tested using ethanol loss-of-righting-reflex (LORR) and 2-bottle choice ethanol consumption assays.

RESULTS

We found that in flies, reduced dLmo activity increased sensitivity to ethanol-induced sedation, whereas increased expression of dLmo led to increased resistance to ethanol-induced sedation. In mice, reduced levels of Lmo3 were correlated with increased sedation time in the LORR test and decreased ethanol consumption in the 2-bottle choice protocol.

CONCLUSIONS

These data describe a novel and conserved role for Lmo genes in flies and mice in behavioral responses to ethanol. These studies also demonstrate the feasibility of rapidly translating findings from invertebrate systems to mammalian models of alcohol abuse by combining RNA interference in transgenic mice and behavioral testing.

Authors+Show Affiliations

Ernest Gallo Clinic and Research Center, University of California at San Francisco, California, USA. alasek@gallo.ucsf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

21599714

Citation

Lasek, Amy W., et al. "Lmo Genes Regulate Behavioral Responses to Ethanol in Drosophila Melanogaster and the Mouse." Alcoholism, Clinical and Experimental Research, vol. 35, no. 9, 2011, pp. 1600-6.
Lasek AW, Giorgetti F, Berger KH, et al. Lmo genes regulate behavioral responses to ethanol in Drosophila melanogaster and the mouse. Alcohol Clin Exp Res. 2011;35(9):1600-6.
Lasek, A. W., Giorgetti, F., Berger, K. H., Tayor, S., & Heberlein, U. (2011). Lmo genes regulate behavioral responses to ethanol in Drosophila melanogaster and the mouse. Alcoholism, Clinical and Experimental Research, 35(9), pp. 1600-6. doi:10.1111/j.1530-0277.2011.01506.x.
Lasek AW, et al. Lmo Genes Regulate Behavioral Responses to Ethanol in Drosophila Melanogaster and the Mouse. Alcohol Clin Exp Res. 2011;35(9):1600-6. PubMed PMID: 21599714.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lmo genes regulate behavioral responses to ethanol in Drosophila melanogaster and the mouse. AU - Lasek,Amy W, AU - Giorgetti,Francesco, AU - Berger,Karen H, AU - Tayor,Stacy, AU - Heberlein,Ulrike, Y1 - 2011/05/20/ PY - 2011/5/24/entrez PY - 2011/5/24/pubmed PY - 2012/3/1/medline SP - 1600 EP - 6 JF - Alcoholism, clinical and experimental research JO - Alcohol. Clin. Exp. Res. VL - 35 IS - 9 N2 - BACKGROUND: Previous work from our laboratory demonstrated a role for the Drosophila Lim-only (dLmo) gene in regulating behavioral responses to cocaine. Herein, we examined whether dLmo influences the flies' sensitivity to ethanol's sedating effects. We also investigated whether 1 of the mammalian homologs of dLmo, Lmo3, is involved in behavioral responses to ethanol in mice. METHODS: To examine dLmo function in ethanol-induced sedation, mutant flies with reduced or increased dLmo expression were tested using the loss of righting (LOR) assay. To determine whether mouse Lmo3 regulates behavioral responses to ethanol, we generated transgenic mice expressing a short-hairpin RNA targeting Lmo3 for RNA interference-mediated knockdown by lentiviral infection of single cell embryos. Adult founder mice, expressing varying amounts of Lmo3 in the brain, were tested using ethanol loss-of-righting-reflex (LORR) and 2-bottle choice ethanol consumption assays. RESULTS: We found that in flies, reduced dLmo activity increased sensitivity to ethanol-induced sedation, whereas increased expression of dLmo led to increased resistance to ethanol-induced sedation. In mice, reduced levels of Lmo3 were correlated with increased sedation time in the LORR test and decreased ethanol consumption in the 2-bottle choice protocol. CONCLUSIONS: These data describe a novel and conserved role for Lmo genes in flies and mice in behavioral responses to ethanol. These studies also demonstrate the feasibility of rapidly translating findings from invertebrate systems to mammalian models of alcohol abuse by combining RNA interference in transgenic mice and behavioral testing. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/21599714/Lmo_genes_regulate_behavioral_responses_to_ethanol_in_Drosophila_melanogaster_and_the_mouse_ L2 - https://doi.org/10.1111/j.1530-0277.2011.01506.x DB - PRIME DP - Unbound Medicine ER -