Since histone demethylases and other chromatin-remodeling enzymes are known to play a role in the development of addiction, ethanol-related phenotypes have been characterized for the 13 Jumonji (JmjC) domain-containing histone demethylase genes in Drosophila. For 5 of the genes loss-of-function mutations result in atypical alcohol response phenotypes: JHDM2 (ortholog of 4 human genes, including KDM3A, KDM3B and JMJD1C), lid (ortholog of 4 human KDM5 genes), NO66 (ortholog of human RIOX1 and RIOX2), HSPBAP1 (ortholog of human HSPBAP1), and JMJD7 (ortholog of human JMJD7).
None of the orthologous human genes has been introduced into flies.
Phenotypes observed for loss-of-function mutations of the 5 Drosophila genes involve various combinations of changes in sensitivity and tolerance: increased sensitivity and reduced tolerance (JHDM2), increased sensitivity and normal tolerance (NO66), increased sensitivity and increased tolerance (lid), normal or slightly reduced sensitivity and reduced tolerance (HSPBAP1 and JMJD7). Targeted knockdown in the nervous system effected by pan-neuronal RNAi was performed for JHDM2, lid, and NO66; phenotypes similar to those for loss-of-function mutations were observed.
[updated Jul. 2018 by FlyBase; FBrf0222196]