The serotonin (5-HT) receptor antagonist metitepine has been shown to suppress feeding in flies; it was initially identified in a high-throughput feeding assay using Drosophila first-instar larvae to screen for drugs that modify food intake. There are five identified G-protein-coupled 5-HT receptors in flies; all five show sensitivity to metitepine in a human cell-culture assay. However, when loss-of-function mutations of each are assessed in the larval feeding assay, only mutants in the Dmel\5-HT2A receptor gene exhibit resistance to the feeding-suppressive effects of the drug. RNAi-targeting constructs, alleles caused by insertional mutagenesis, and an amorphic allele created by targeted recombination have been generated for Dmel\5-HT2A.
Dmel\5-HT2A is orthologous to three serotonin class 2 receptor genes in human, HTR2A, HTR2B, and HTR2C. HTR2A is implicated in susceptibility to a number of disorders related to mental health, including obsessive-compulsive disorder, depressive disorders, and anorexia nervosa (see MIM:182135). Of the human HTR2 genes, only Hsap\HTR2C has been introduced into flies; a stock is available but has not been characterized.
There is a second serotonin class 2 receptor gene in flies, Dmel\5-HT2B. Both Dmel\5-HT2A and Dmel\5-HT2B have been characterized as modulators of anxiety in a fly assay. Similar to the case for resistance to metitepine, the two genes exhibit different responses: knockdown of 5-HT2B is observed to significantly decrease behavior associated with anxiety; knockdown of 5-HT2A has no consistent effect. See the human disease model reports 'anxiety modulator(s), serotonin class 2 receptor(s)' (FBhh0001006) and 'anxiety modulators, fly wall-following model' (FBhh0001005).
Animals homozygous for loss-of-function mutations of Dmel\5-HT2A typically die during late embryonic or early larval stages. In the larval feeding assay (in absence of metitepine), first-instar larvae homozygous for 5-HT2A loss-of-function mutations eat less than controls.
[updated Jun. 2022 by FlyBase; FBrf0222196]
Obesity is an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. Obesity is associated with increased risk of illness, disability, and death. (http://medical-dictionary.thefreedictionary.com/obesity).
The development of obesity is recognized as having both genetic and environmental components (https://www.sciencelearn.org.nz/resources/203-obesity-genetic-or-environmental).
Variants in the human HTR2A gene are associated with susceptibility to schizophrenia, obsessive-compulsive disorder, and other psychiatric conditions; variants in this gene also affect response to specific antidepressants. [NCBI Gene, HTR2A, 2019.04.17; MIM:182135, 2019.04.17]
There are 13 G-protein-coupled serotonin receptor genes in human, comprising 6 subclasses (HGNC: https://www.genenames.org/data/genegroup/#!/group/170). There are three human serotonin class 2 receptor genes.
There are 5 G-protein-coupled serotonin receptor genes in Drosophila, making up 3 subclasses (corresponding to subclasses 1, 2 and 7 in human) (see FBgg0000206). There are two serotonin class 2 receptor genes in fly.
HTR2A, HTR2B, and HTR2C encode G-protein-coupled receptors for the neurotransmitter 5-hydroxytryptamine (5-HT or serotonin).
