The Lowe Oculocerebrorenal Syndrome (OCRL; McKusick #309000) is an X-linked disorder characterized by mental retardation, congenital cataracts, renal tubular dysfunction in childhood and progressive renal failure in adulthood. We have demonstrated that the OCRL gene product encodes a phosphatidylinositol (4,5)bisphosphate 5 phosphatase and that fibroblasts from OCRL patients are deficient in this enzymatic activity. The protein defective in OCRL is localized to the Golgi, most likely in the trans-Golgi network. Although the physiological functions of most inositol phosphates are incompletely understood, phosphatidylinositol (4,5) bisphosphate is clearly involved in signal transduction and, in particular, is implicated in regulating Golgi vesicle formation. In order to pursue our investigation of Golgi function in OCRL, we have created a mouse that lacks the OCRL1 gene product by deletion of exons encoding the carboxyl terminus of the protein. Surprisingly, mice lacking OCRL1 do NOT have congenital cataracts and have no renal or nervous system functional abnormalities. We have also created mice lacking a related, highly homologous autosomal phosphatidylinositol (4,5) bisphosphate 5 phosphatase, which are also viable and grossly normal phenotypically. We are now mating these mice to create mice lacking both enzymatic activities.
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