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.
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]