Fly orthologs of candidate anxiety genes found at quantitative trait loci (QTLs) identified from a mouse genetic experiment were screened using the fly wall-following assay (WAFO, see FBhh0001005). Of 17 fly genes test, 4 exhibited alterations in the WAFO assay, including Dmel\CCKLR-17D1 and Dmel\CCKLR-17D3. Knockdown of either gene resulted in reduced WAFO (interpreted as decreased anxiety). These 2 paralogous genes are orthologous to a pair of human genes, CCKAR and CCKBR. The genes encode G-protein-coupled receptors that bind neuropeptide ligands, in the case of human the CCK neuropeptide. In mammals, type B receptors are thought to regulate anxiety, arousal, neuroleptic activity, and opiate-induced analgesia.
Neither human CCK receptor gene has been introduced into flies.
RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for both Dmel\CCKLR-17D1 and Dmel\CCKLR-17D3. A small number of genetic and physical interactions have been described for Dmel\CCKLR-17D1. See below and in the CCKLR-17D1 and CCKLR-17D3 gene reports.
[updated Apr. 2019 by FlyBase; FBrf0222196]