Open AccessDrosophila carrying epilepsy-associated variants in the vitamin B6 metabolism gene PNPO display allele- and diet-dependent phenotypes
Author(s) -
Wanhao Chi,
Atulya Iyengar,
Wenqin Fu,
Wei Liu,
Abigayle Berg,
Chun Fang Wu,
Xiaoxi Zhuang
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2115524119
Subject(s) - allele , epilepsy , biology , phenotype , genetics , gene , neuroscience
Significance Both genetic and environmental factors contribute to epilepsy. Understanding their contributions and interactions helps disease management. However, it is often challenging to study gene–environment interaction in humans due to their heterogeneous genetic background and less controllable environmental factors. The fruit fly,Drosophila melanogaster , has been proven to be a powerful model to study human diseases, including epilepsy. We generated knock-in flies carrying different epilepsy-associated pyridox(am)ine 5′ -phosphate oxidase (PNPO ) alleles and studied the developmental, behavioral, electrophysiological, and fitness effects of each mutant allele under different dietary conditions. We showed that phenotypes in knock-in flies are allele and diet dependent, providing clues for timely and specific diet interventions. Our results offer biological insights into mechanisms underlying phenotypic variations and specific therapeutic strategies.