This report describes characterization of the fly alcohol response using the Drosophila gene RhoGAP18B, which is a Rho GTPase activating protein. Although there are multiple members of this gene family in both flies and human, RhoGAP18B is not a moderate- or high-scoring ortholog of any of the human genes. Loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\RhoGAP18B.
In a genetic screen for insertion mutations the result in altered sensitivity to ethanol, an allele of RhoGAP18B showed resistance to ethanol-induced sedation. As in most organisms, in wild-type flies low ethanol doses induce increased activity, while high doses are sedating. Different isoforms of RhoGAP18B appear to regulate the stimulant vs. the sedating effects. Genetic and physical interactions for Dmel\RhoGAP18B have been described; see below and in the RhoGAP18B gene report.
[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]
Rho GTPase activating proteins (RhoGAPs or ARHGAPs) bind to and stimulate the GTPase activity of Rho family small GTPases (Rho GTPase activating proteins (ARHGAP); https://www.genenames.org/cgi-bin/genefamilies/set/721).
RhoGAP domain-containing proteins usually function to catalyze the hydrolysis of GTP that is bound to RHO, RAC and/or CDC42, inactivating these regulators of the actin cytoskeleton (Peck et al., 2002; pubmed:12297274) and thus impacting signaling pathways modulated by cytoskeletal changes.
Very low-scoring ortholog of some human Rho GTPase activating proteins (RhoGAPs); multiple members of this gene family in both flies and human.
