Janice Chou's Section on Cellular Differentiation studies glycogen storage disease type I (GSD-I), which is caused by deficiencies in the glucose-6-phosphatase-alpha (G6Pase-alpha)–glucose-6-phosphate transporter (G6PT) complex. The deficiencies result in disturbed glucose homeostasis; GSD-Ib also presents with myeloid dysfunctions. Chou showed that an increase in cellular cholesterol efflux and antioxidant capacity in the sera of GSD-Ia patients may protect against premature atherosclerosis. Using G6PT−/− mice, the Section showed that myeloid dysfunctions in GSD-Ib are intrinsically linked to G6PT deficiency in the bone marrow and neutrophils and that an adenoviral vector–mediated gene transfer improved metabolic and myeloid functions. The Section has recently characterized a G6Pase-alpha isoform, G6Pase-beta, that is expressed ubiquitously, as is G6PT. The Section showed that G6Pase-beta–null mice manifest myeloid dysfunctions mimicking GSD-Ib and that G6Pase-beta–deficient neutrophils undergo ER stress and an enhanced rate of apoptosis. The results demonstrate that a functional G6Pase-beta–G6PT complex is critical for neutrophil function, defining a molecular pathway to neutropenia and neutrophil dysfunction of unknown etiology.
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