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Identification of quantitative trait loci and candidate genes for an anxiolytic‐like response to ethanol in BXD recombinant inbred strains

Year: 2016
Type: article
Abstract: Genetic differences in acute behavioral responses to ethanol contribute to the susceptibility to alcohol use disorder and the reduction of anxiety is a commonly reported motive underlying ethanol consumption among alcoholics. Therefore, we studied the genetic variance in anxiolytic-like responses to ethanol across the BXD recombinant inbred (RI) mouse panel using the light-dark transition model of anxiety. Strain-mean genetic mapping and a mixed-model quantitative trait loci (QTL) analysis replicated several previously published QTL for locomotor activity and identified several novel anxiety-related loci. Significant loci included a chromosome 11 saline anxiety-like QTL (Salanq1) and a chromosome 12 locus (Etanq1) influencing the anxiolytic-like response to ethanol. Etanq1 was successfully validated by studies with BXD advanced intercross strains and fine-mapped to a region comprising less than 3.5 Mb. Through integration of genome-wide mRNA expression profiles of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens and ventral midbrain) across the BXD RI panel, we identified high priority candidate genes within Etanq1, the strongest of which was Ninein (Nin), a Gsk3β-interacting protein that is highly expressed in the brain.
DOI: 10.1111/gbb.12289
Authors: A. H. Putman, A. R. Wolen, J. L. Harenza, R. K. Yordanova, B. T. Webb, E. J. Chesler, M. F. Miles
Language: English
Subfield: Genetics
Open Access status: green
Funders: National Institutes of Health, National Institutes of Natural Sciences, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Center for Advancing Translational Sciences
Awards: Genetic and genomic analysis of ethanol anxiolysis, Functional genomics of ethanol craving and naltrexone, Data Structures, Algorithms and Tools for Ontological Discovery, Cross-species genetic analysis of ethanol-related behavior, Of Mice and Primates: Gene Networks in Excessive Ethanol Consumption and Anxiety, Center for Clinical and Translational Research, Cross Species Characterization of Gene Networks in Acute Responses to Ethanol, G716289812, Training in the pharmacology of abused drugs, Cross-species investigation of gene networks for ethanol-related behaviors, ResearchTraining: Psychiatric and Statistical Genetics, Cancer Center Support (CORE) Grant
OpenAlex ID: W2294907207
FWCI: 2.013
Cites: 84
Cited by: 21
Related to: 10