Isolation of the gene for murine glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1A

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 c...

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Bibliographic Details
Published in:The Journal of biological chemistry 1993-10, Vol.268 (29), p.21482-21485
Main Authors: Shelly, L L, Lei, K J, Pan, C J, Sakata, S F, Ruppert, S, Schutz, G, Chou, J Y
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Cells, Cultured
DNA, Complementary
Glucose-6-Phosphatase - genetics
Glucose-6-Phosphatase - metabolism
Glycogen Storage Disease Type I - enzymology
Humans
Hydrolysis
Kinetics
Mice
Mice, Mutant Strains
Microsomes, Liver - enzymology
Molecular Sequence Data
RNA, Messenger - metabolism
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1016/s0021-9258(20)80563-8