title: Isolation of the gene for murine glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1A.
abstract: Glycogen storage disease (GSD) type 1a (von Gierke disease) is caused by a deficiency in glucose-6-phosphatase, the key enzyme in glucose homeostasis catalyzing the terminal step in gluconeogenesis and glycogenolysis. Despite its clinical importance, this membrane-bound enzyme has eluded molecular characterization. Here we report the cloning and characterization of a murine glucose-6-phosphatase cDNA by screening a mouse liver cDNA library differentially with mRNA populations representing the normal and the albino deletion mouse known to express markedly reduced glucose-6-phosphatase activity. Additionally, we identified the gene that consists of 5 exons. Biochemical analyses indicate that the in vitro expressed enzyme is indistinguishable from mouse liver microsomal glucose-6-phosphatase exhibiting essentially identical kinetic constants, latency, thermal lability, and vanadate sensitivity. The characterization of the murine glucose-6-phosphatase gene opens the way for studying the molecular basis of GSD type 1a in humans and its etiology in an animal model.
authors.affiliation: Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: L L
authors.initials: LL
authors.lastname: Shelly
authors.forename: K J
authors.initials: KJ
authors.lastname: Lei
authors.forename: C J
authors.initials: CJ
authors.lastname: Pan
authors.forename: S F
authors.initials: SF
authors.lastname: Sakata
authors.forename: S
authors.initials: S
authors.lastname: Ruppert
authors.forename: G
authors.initials: G
authors.lastname: Schutz
authors.forename: J Y
authors.initials: JY
authors.lastname: Chou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary; D005952:Glucose-6-Phosphatase / Q000235:genetics* / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000201:enzymology*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D051379:Mice; D008817:Mice, Mutant Strains; D008862:Microsomes, Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D005952:Glucose-6-Phosphatase