Based on GWAS findings that implicate human MEF2B in variability in response to alcohol, phenotypes of the Drosophila Mef2 gene were characterized. There are multiple MEF2's in human: Dmel\Mef2 is orthologous to MEF2A, MEF2C, MEF2D, and MEF2B. For the fly Mef2 gene, an amorphic allele, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
None of the human MEF2 genes has been introduced into flies.
Flies with loss-of-function mutations in Dmel\Mef2 exhibit decreased EtOH sedation sensitivity; pan-neuronal knockdown of Dmel\Mef2 expression, effected by RNAi, also makes flies resistant to EtOH sedation.
In contrast, in independent experiments, decreased ethanol tolerance was observed upon expression of a dominant-negative allele of Mef2, either pan-neuronally or specifically in the mushroom body α/β neurons. Based on the observation that mammalian homologs of Dmel\Hr38 are transcriptionally induced by the MEF2 transcription factors, expression of Hr38 was assessed. It was found that acute ethanol exposure induces transient expression of Hr38 and other immediate early neuronal activity genes in flies, and that this response is dependent upon Mef2.
[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 MEF2 proteins are members of the MADS/MEF2 family of DNA binding proteins; they are transcription activators which bind specifically to the MEF2 element present in the regulatory regions of numerous muscle-specific, growth factor- and stress-induced genes. Members of this family are involved in control of muscle and neuronal cell differentiation and development, and are regulated by class II histone deacetylases [Gene Cards, MAEF2A, MEF2B, MEF2C, MEF2D; 2019.10.21]
Many to one: 4 human to 1 Drosophila.
Many to one: 4 human to 1 Drosophila.
Many to one: 4 human to 1 Drosophila.
Many to one: 4 human to 1 Drosophila.
Moderate- to low-scoring ortholog of human MEF2A, MEF2C, MEF2D, and MEF2B (1 Drosophila to 4 human). Dmel\Mef2 shares 32-43% identity and 43-56% similarity with the human genes.
