The OCRL gene product is only one of many enzymes implicated in the metabolism of phosphatidlyinositols involved in a variety of important but incompletely understood cellular signaling pathways. Mutations in genes involved in these pathways would contribute to our understanding of the functional significance and inter-relationships of these different phospholipid signaling pathways. The laboratory is beginning a systematic program to isolate and delete the genes encoding enzymes in phosphatidylinositol phosphate metabolism using knock-out technology in embryonal stem cells to create mice deficient in these enzymatic activities. Embryonal stem cells heterozygous for a null mutation in the isoform of phosphatidylinositol bisphosphate-3 hydroxy kinase have been created and are being injected into blastocysts to create mice carrying this mutation. Similar experiments involving the a-isoform are in progress.
