Myo‐inositol catabolism in Drosophila melanogaster: implications for diabetes and development

Abstract

Myo‐inositol is a six‐carbon sugar that can serve as a carbon/energy source, an osmolyte, and a precursor of phospholipids. It has been suggested to play a pivotal role in diabetes mellitus. High levels of the myo‐inositol catabolic gene product, myo‐inositol oxygenase (MIOX), has been seen in diabetic tissues. More than 75% of genes involved in human diseases have orthologs in the model organism Drosophila melanogaster. This study identified the D. melanogaster MIOX gene using bioinformatic and molecular genetic tools. This gene is located on chromosome 3L, and has 4 exons and 3 introns. The predicted protein is 33 kDa and is 52.2% identical (67.7% similar) to human MIOX. In silico experiments have also revealed many upstream regulatory sequences responsive to inositol, osmotic and/or oxidative stress. To determine if perturbation of this gene results in a developmental phenotype, D. melanogaster mutant strains heterozygous for a P‐element insertion into MIOX gene were crossed. Preliminary results suggest that homozygotes with disrupted MIOX genes are viable on rich media. Another component of this study was to determine where the MIOX gene product is localized throughout development. Preliminary data from western blots, confocal microscopy, and immunohistochemistry, indicates that MIOX may be located in the gut/malpighian tubule region.