This report describes characterization of the fly alcohol response using the Drosophila gene homer. Dmel\homer acts as an adaptor protein that binds metabotropic glutamate receptors and other intracellular signaling proteins. The single fly gene is orthologous to 3 genes in human; it is most closely related to HOMER2. HOMER2 is implicated in a form of autosomal dominant deafness. Classic loss-of-function mutations, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\homer.
UAS constructs of the human Hsap\HOMER2 and Hsap\HOMER1 genes have been introduced into flies, but have not been characterized in context of this model.
Mutations in Dmel\homer produce a variety of behavioral phenotypes, including sleep defective, hyperactivity, and stress response defective. In microarray experiments, significant and reproducible decreases in Dmel\homer mRNA expression were observed in response to a single or multiple ethanol exposures. Animals homozygous for an amorphic mutation of Dmel\homer exhibit increased ethanol sensitivity and reduced development of rapid tolerance upon multiple exposures. Pan-neuronal expression of wild-type homer rescues both ethanol sensitivity and rapid tolerance phenotypes. This observation has been refined to determine that both phenotypes are rescued by the expression of wild-type homer in a subset of neurons that include the ellipsoid body of the adult brain.
[updated Oct. 2019 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]
Members of the homer family are dendritic postsynaptic density scaffold proteins that regulate group 1 metabotrophic glutamate receptor function. [Gene Cards, HOMER2, HOMER1, HOMER3; 2018.01.11]
Many to one: 3 human to 1 Drosophila; the 3 human genes are HOMER1, HOMER2, and HOMER3.
Many to one: 3 human to 1 Drosophila; the 3 human genes are HOMER1, HOMER2, and HOMER3.
Many to one: 3 human to 1 Drosophila; the 3 human genes are HOMER1, HOMER2, and HOMER3.
High-scoring ortholog of human HOMER2; moderate-scoring ortholog of HOMER1 and HOMER3 (1 Drosophila to 3 human). Dmel\homer shares 36-42% identity and 50-54% similarity with the human genes.
