Evidence map›Paper›PMID 32090358›Full record

ArticleAlcoholism, clinical and experimental research2020

RNA-Seq Analysis of Genetic and Transcriptome Network Effects of Dual-Trait Selection for Ethanol Preference and Withdrawal Using SOT and NOT Genetic Models.

Laura B Kozell, Denesa Lockwood, Priscila Darakjian, Stephanie Edmunds, Karen Shepherdson, Kari J Buck, Robert Hitzemann

Open access · hybridAbstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
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  4. Identification of novel genetic loci and candidate genes for progressive ethanol consumption in diversity outbred mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Laura B KozellFrom the, Department of Behavioral Neuroscience, VA Portland Health Care System, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0003-3059-2046
Denesa LockwoodFrom the, Department of Behavioral Neuroscience, VA Portland Health Care System, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0002-6406-2783
Priscila DarakjianFrom the, Department of Behavioral Neuroscience, VA Portland Health Care System, Oregon Health & Science University, Portland, Oregon.
Stephanie EdmundsFrom the, Department of Behavioral Neuroscience, VA Portland Health Care System, Oregon Health & Science University, Portland, Oregon.
Karen ShepherdsonFrom the, Department of Behavioral Neuroscience, VA Portland Health Care System, Oregon Health & Science University, Portland, Oregon.
Kari J BuckFrom the, Department of Behavioral Neuroscience, VA Portland Health Care System, Oregon Health & Science University, Portland, Oregon.
Robert HitzemannFrom the, Department of Behavioral Neuroscience, VA Portland Health Care System, Oregon Health & Science University, Portland, Oregon.
VA Portland Health Care System · US

Funding

Translational measures of risk for excessive alcohol consumptionP60AA010760 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI TAMARA J. PHILLIPS · 2006 to 2026
$34.5M
Neurocircuitry Mapping and Genotyping CoreU01AA013484 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI HITZEMANN, ROBERT J. · 2001 to 2021
$6.2M
The Role of Mpdz in Ethanol Withdrawal and Genetically Correlated BehaviorsR01AA011114 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI BUCK, KARI J · 2000 to 2020
$4.3M
Mouse Genetic Models for Alcohol ResearchR24AA020245 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI PHILLIPS, TAMARA J. · 2011 to 2020
$2.3M
NIAAA NIH HHS P60 AA010760NIAAA NIH HHS R01 AA011114NIAAA NIH HHS R01AA011114NIAAA NIH HHS R24 AA020245NIAAA NIH HHS R24AA020245NIAAA NIH HHS U01 AA013484U.S. Department of Veterans Affairs BX00022
6 · The paper itself

Abstract

backgroundGenetic factors significantly affect alcohol consumption and vulnerability to withdrawal. Furthermore, some genetic models showing predisposition to severe withdrawal are also predisposed to low ethanol (EtOH) consumption and vice versa, even when tested independently in naïve animals.

methodsBeginning with a C57BL/6J × DBA/2J F2 intercross founder population, animals were simultaneously selectively bred for both high alcohol consumption and low acute withdrawal (SOT line), or vice versa (NOT line). Using randomly chosen fourth selected generation (S4) mice (N = 18-22/sex/line), RNA-Seq was employed to assess genome-wide gene expression in ventral striatum. The MegaMUGA array was used to detect genome-wide genotypic differences. Differential gene expression and the weighted gene co-expression network analysis were implemented as described elsewhere (Genes Brain Behav 16, 2017, 462).

resultsThe new selection of the SOT and NOT lines was similar to that reported previously (Alcohol Clin Exp Res 38, 2014, 2915). One thousand eight hundred and sixteen transcripts were detected as differentially expressed between the lines. For genes more highly expressed in the SOT line, there was enrichment in genes associated with cell adhesion, synapse organization, and postsynaptic membrane. The genes with a cell adhesion annotation included 23 protocadherins, Mpdz and Dlg2. Genes with a postsynaptic membrane annotation included Gabrb3, Gphn, Grid1, Grin2b, Grin2c, and Grm3. The genes more highly expressed in the NOT line were enriched in a network module (red) with annotations associated with mitochondrial function. Several of these genes were module hub nodes, and these included Nedd8, Guk1, Elof1, Ndufa8, and Atp6v1f.

conclusionsMarked effects of selection on gene expression were detected. The NOT line was characterized by higher expression of hub nodes associated with mitochondrial function. Genes more highly expressed in the SOT aligned with previous findings, for example, Colville and colleagues (Genes Brain Behav 16, 2017, 462) that both high EtOH preference and consumption are associated with effects on cell adhesion and glutamate synaptic plasticity.

Indexed as

Behavior, AnimalAlcohol DrinkingAnimalsCentral Nervous System DepressantsEthanolGene Expression ProfilingGuanylate KinasesMembrane ProteinsMiceModels, GeneticNADH DehydrogenaseNEDD8 ProteinProtocadherinsReceptors, GABA-AReceptors, GlutamateReceptors, Metabotropic GlutamateCentral Nervous System DepressantsDlg2 protein, mouseEthanolGabrb3 protein, mouseglutamate receptor delta 1Guanylate KinasesMembrane Proteinsmetabotropic glutamate receptor 3Mpdz protein, mouseNADH DehydrogenaseNEDD8 ProteinNR2B NMDA receptorNR2C NMDA receptorProtocadherinsReceptors, GABA-AReceptors, GlutamateReceptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateVacuolar Proton-Translocating ATPasesAlcoholDual-Trait Selective BreedingGeneticsMouseRNA-SeqTranscriptome SequencingVentral StriatumWeighted Gene Co-expression Network Analysis

Identifiers

PMID32090358
PMCPMC7169974
OpenAlexW3008301536

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.