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General Information
Name
alcohol, response to, EPS8-related
FlyBase ID
FBhh0000688
OMIM
Overview

This report describes characterization of the fly response to alcohol using the Drosophila gene arouser (aru). Dmel\aru is an SH3 adaptor protein with orthology to the four EPS8 (Epidermal Growth Factor Receptor Pathway Substrate 8) and EPS8-like genes in human. RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\aru. There is a second gene from this family in Drosophila, CG8907.

One of the human EPS8 genes, Hsap\EPS8L2, has been introduced into flies, but has not been characterized.

In a genetic screen for mutants with altered sensitivity to ethanol sedation, an insertion allele of aru exhibited increased ethanol sensitivity; a second insertion allele was also found to have an increased sensitivity phenotype. Both alleles produce a sensitivity phenotype in heterozygous animals. A small number of genetic and physical interactions have been described for Dmel\aru; see below and in the aru gene report.

Since the human EPS8 genes are implicated in both EGFR/ERK and P13K/AKT signaling pathways, additional mutations in Drosophila genes within these pathways have been assessed for ethanol sensitivity; see FBhh0000685 and FBhh0000689.

[updated Jan. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: alcohol use disorder, susceptibility to (fly models overview)
Symptoms and phenotype

Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).

The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)

Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).

Alcoholism is a multifactorial, genetically influenced disorder. [from OMIM:103780; 2017.12.19]

Specific Disease Summary: alcohol, response to, EPS8-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

EPS8 genes that have been characterized are signaling adapters that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on their association with other signal transducers, can regulate different processes. [Gene Cards, EPS8; 2018.01.05]

External links
Disease synonyms
AUD susceptibility, EPS8-related
Search term: alcohol use disorder
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: 4 human to 2 Drosophila. The human genes are EPS8L2, EPS8, EPS8L1 and EPS8L3.

Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: 4 human to 2 Drosophila. The human genes are EPS8L2, EPS8, EPS8L1 and EPS8L3.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    arouser (aru) encodes an SH3 adaptor protein that interacts with Egfr and PI3K pathways. Its roles include regulation of synapse number, memory formation and ethanol sedation sensitivity. [Date last reviewed: 2019-03-07]
    Molecular function (GO)
    Cellular component (GO)
    Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate-scoring ortholog of human EPS8L2 and EPS8; lower-scoring ortholog of EPS8L1 and EPS8L3 (2 Drosophila to 4 human). Dmel\aru shares 27-28% identity and 41% similarity with EPS8L2, EPS8, and EPS8L1.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (3 groups)
        protein-protein
        Interacting group
        Assay
        References
        pull down, autoradiography, anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        experimental knowledge based
        Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)
        Models Based on Experimental Evidence ( 3 )
        Modifiers Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Interaction
        References
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        P-element activity
        References (6)