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]
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 MIM:103780; 2017.12.19]
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]
Many to many: 4 human to 2 Drosophila. The human genes are EPS8L2, EPS8, EPS8L1 and EPS8L3.
Many to many: 4 human to 2 Drosophila. The human genes are EPS8L2, EPS8, EPS8L1 and EPS8L3.
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.
