Drosophila mutants lacking the core autophagy gene Atg16 exhibit increased resistance to the sedative effects of ethanol; this phenotype is not observed for null mutants of other autophagy genes tested. Dmel\Atg16 is orthologous to two genes in human, ATG16L1 and ATG16L2; it is more closely related to ATG16L1. RNAi targeting constructs, alleles caused by insertional mutagenesis, and loss-of-function mutations caused by imprecise excision of TE insertions have been generated for Dmel\Atg16.
Neither human gene, ATG16L1 or ATG16L2, has been introduced into flies.
Dmel\Atg16 loss-of-function mutations exhibit defects in autophagy, resulting in related phenotypes, including reduced lifespan and neuromuscular dysfunction. Unexpectedly, Atg16 mutant animals are much more resistant to sedation upon exposure to ethanol than control flies. The Atg16 function in ethanol sensitivity maps to Corazonin-producing neurosecretory cells; Atg16 deficiency impairs production of the Corazonin (Crz) neuropeptide. (See human disease model report 'alcohol, response to, Crz neuropeptide-related' FBhh0001120).
[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]
The protein encoded by ATG16L1 is part of a large protein complex that is necessary for autophagy (the major process by which intracellular components are targeted to lysosomes for degradation). Little is known about ATG16L2, which may have a similar function. [Gene Cards, ATG16L1 and ATG16L2; 2019.20.22]
Many to one: 2 human to 1 Drosophila.
Many to one: 2 human to 1 Drosophila.
High-scoring ortholog of ATG16L1; moderate-scoring ortholog of ATG16L2 (1 Drosophila to 2 human). Dmel\Atg16 shares 30-38% identity and 47-60% similarity with the human genes.
