Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies

Alcohol use disorders are influenced by many interacting genetic and environmental factors. Highlighting this complexity is the observation that large genome-wide association experiments have implicated many genes with weak statistical support. Experimental model systems, cell culture and animal, ha...

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Main Authors:	Joslyn, Geoff, Wolf, Fred W., Brush, Gerry, Wu, Lianqun, Schuckit, Marc, White, Raymond L.
Format:	Online
Language:	English
Published:	Genetics Society of America 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276178/

id	pubmed-3276178
recordtype	oai_dc
spelling	pubmed-32761782012-03-01 Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies Joslyn, Geoff Wolf, Fred W. Brush, Gerry Wu, Lianqun Schuckit, Marc White, Raymond L. Investigation Alcohol use disorders are influenced by many interacting genetic and environmental factors. Highlighting this complexity is the observation that large genome-wide association experiments have implicated many genes with weak statistical support. Experimental model systems, cell culture and animal, have identified many genes and pathways involved in ethanol response, but their applicability to the development of alcohol use disorders in humans is undetermined. To overcome the limitations of any single experimental system, the analytical strategy used here was to identify genes that exert common phenotypic effects across multiple experimental systems. Specifically, we (1) performed a mouse linkage analysis to identify quantitative trait loci that influence ethanol-induced ataxia; (2) performed a human genetic association analysis of the mouse-identified loci against ethanol-induced body sway, a phenotype that is not only comparable to the mouse ethanol-ataxia phenotype but is also a genetically influenced endophenotype of alcohol use disorders; (3) performed behavioral genetic experiments in Drosophila showing that fly homologs of GPC5, the member of the glypican gene family implicated by both the human and mouse genetic analyses, influence the fly’s response to ethanol; and (4) discovered data from the literature demonstrating that the genetically implicated gene’s expression is not only temporally and spatially consistent with involvement in ethanol-induced behaviors but is also modulated by ethanol. The convergence of these data provides strong support to the hypothesis that GPC5 is involved in cellular and organismal ethanol response and the etiology of alcohol use disorders in humans. Genetics Society of America 2011-12-01 /pmc/articles/PMC3276178/ /pubmed/22384374 http://dx.doi.org/10.1534/g3.111.000976 Text en Copyright © 2011 Joslyn et al http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Joslyn, Geoff Wolf, Fred W. Brush, Gerry Wu, Lianqun Schuckit, Marc White, Raymond L.
spellingShingle	Joslyn, Geoff Wolf, Fred W. Brush, Gerry Wu, Lianqun Schuckit, Marc White, Raymond L. Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies
author_facet	Joslyn, Geoff Wolf, Fred W. Brush, Gerry Wu, Lianqun Schuckit, Marc White, Raymond L.
author_sort	Joslyn, Geoff
title	Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies
title_short	Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies
title_full	Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies
title_fullStr	Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies
title_full_unstemmed	Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies
title_sort	glypican gene gpc5 participates in the behavioral response to ethanol: evidence from humans, mice, and fruit flies
description	Alcohol use disorders are influenced by many interacting genetic and environmental factors. Highlighting this complexity is the observation that large genome-wide association experiments have implicated many genes with weak statistical support. Experimental model systems, cell culture and animal, have identified many genes and pathways involved in ethanol response, but their applicability to the development of alcohol use disorders in humans is undetermined. To overcome the limitations of any single experimental system, the analytical strategy used here was to identify genes that exert common phenotypic effects across multiple experimental systems. Specifically, we (1) performed a mouse linkage analysis to identify quantitative trait loci that influence ethanol-induced ataxia; (2) performed a human genetic association analysis of the mouse-identified loci against ethanol-induced body sway, a phenotype that is not only comparable to the mouse ethanol-ataxia phenotype but is also a genetically influenced endophenotype of alcohol use disorders; (3) performed behavioral genetic experiments in Drosophila showing that fly homologs of GPC5, the member of the glypican gene family implicated by both the human and mouse genetic analyses, influence the fly’s response to ethanol; and (4) discovered data from the literature demonstrating that the genetically implicated gene’s expression is not only temporally and spatially consistent with involvement in ethanol-induced behaviors but is also modulated by ethanol. The convergence of these data provides strong support to the hypothesis that GPC5 is involved in cellular and organismal ethanol response and the etiology of alcohol use disorders in humans.
publisher	Genetics Society of America
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276178/
_version_	1611505152141819904

Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies

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