Disruption of , a Gene Encoding -Inositol Phosphate Synthase, Causes Male Sterility in

Inositol is a precursor for the phospholipid membrane component phosphatidylinositol (PI), involved in signal transduction pathways, endoplasmic reticulum stress, and osmoregulation. Alterations of inositol metabolism have been implicated in human reproductive issues, the therapeutic effects of drugs used to treat epilepsy and bipolar disorder, spinal cord defects, and diseases including diabetes and Alzheimer's. The sole known inositol synthetic enzyme is -inositol synthase (MIPS), and the homolog in is encoded by the gene. Three identical deletion strains ( /CyO) were constructed, confirmed by PCR and sequencing, and homozygotes / ) were shown to lack the transcript encoding the MIPS enzyme. Without inositol, homozygous deletion fertilized eggs develop only to the first-instar larval stage. When transferred as pupae to food without inositol, however, homozygotes die significantly sooner than wild-type flies. Even with dietary inositol the homozygous males are sterile. An allele, with a -element inserted into the first intron, fails to complement this male sterile phenotype. An additional copy of the gene inserted into another chromosome rescues all the phenotypes. These genetic and phenotypic analyses establish as an excellent model organism in which to examine the role of inositol synthesis in development and reproduction.