Abstract
We investigated the quantitative expression of the human glucose-6-phosphate translocase gene (G6PT1) and its splicing variants in human tissues. The G6PT1 gene was strongly expressed in liver, kidney and haematopoietic progenitor cells, which might explain major clinical symptoms such as hepatomegaly, nephromegaly and neutropenia in glycogen storage diseases type Ib. Reverse transcriptase-mediated PCR amplification of G6PT1 cDNA revealed several splicing variants in tissue-specific manners. The brain-specific isoform, which has an additional 22 amino acids between exons 6 and 8, was also identified in heart and skeletal muscle. A new splicing variant, although less prominent in quantity and lacking polypeptide loops corresponding to exons 2 and 3, may have a distinct substrate affinity or specificity in leukocytes and haematopoietic progenitors. In conclusion, the G6PT1 gene was expressed in various tissues, and alternative splicing variants exist in tissue-specific manners.
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REFERENCES
Beaudet AL, Anderson DC, Michels VV, Arlon WJ, Lange AJ (1980) Neutropenia and impaired neutrophil migration in type 1B glycogen storage disease. J Pediatr 97: 906–910.
Burchell A, Waddell I (1991) The molecular basis of the hepatic microsomal glucose-6-phosphatase system. Biochim Biophys Acta 1092: 129–137.
Chen Y, Burchell A (1995) Glycogen storage diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edn. New York: McGraw-Hill, 935–965.
Gerin I, Veiga-da-Cunha M, Achouri Y, Collet J-F, Schaftingen EV (1997) Sequence of a putative glucose 6-phosphate translocase, mutated in glycogen storage disease type Ib. FEBS Lett 419: 235–238.
Gerin I, Veiga-da-Cunha M, No IG, Van Schaftingen E (1999) Structure of the gene mutated in glycogen storage disease type 1b. Gene 227: 189–195.
Gibson UE, Heid CA, Williams PM (1996) A novel method for real time quantitative RT-PCR. Genome Res 6: 995–1001.
Gitzelmann R, Bosshard NU (1993) Defective neutrophil and monocyte functions in glycogen storage disease type 1b: a literature review. Eur J Pediatr 152 (supplement 1): S33–38.
Heid CA, Stevens J, Livak KJ, Williams PM(1996) Real time quantitative PCR. Genome Res 6: 986–994.
Ihara K, Kuromaru R, Hara T (1998) Genomic structure of the human glucose-6-phosphate translocase gene and novel mutations in the gene of a Japanese patient with glycogen storage disease type 1b. Hum Genet 103: 493–496.
Ihara K, Takabayashi A, Terasaki K, Hara T (1998) Assignment of the glucose 6-phosphate translocase (G6PT) to human chromosome band 11q23.3 by in situ hybridization. Cytogenet Cell Genet 83: 50–51.
Kure S, Suzuki Y, Matsubara Y, et al (1998) Molecular analysis of glycogen storage disease type 1b: identi¢cation of a prevalent mutation among Japanese patients and assignment of a putative glucose-6-phosphate translocase gene to chromosome 11. Biochem Biophys Res Commun 248: 426–431.
Lachaux A, Boillot O, Stamm D, et al (1993) Treatment with lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) and orthotopic liver transplantation for glycogen storage disease type 1b. J Pediatr 123: 1005–1008.
Lange AJ, Arion WJ, Beaudet AL (1980) Type 1b glycogen storage disease is caused by a defect in the glucose-6-phosphate translocase of the microsomal glucose-6-phosphatase system. J Biol Chem 225: 8381–8384.
Lin B, Annabi B, Hiraiwa H, Pan CJ, Chou JY (1998) Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents. J Biol Chem 273: 31656–31660.
Marcolongo P, Barone V, Priori G, et al (1998) Structure and mutation analysis of the glycogen storage disease type 1b gene. FEBS Lett 436: 247–250.
McCawley LJ, Korchak HM, Douglas SD, et al (1994) In vitro and in vivo e¡ects of granulocyte colony-stimulating factor on neutrophils in glycogen storage disease type 1b: granulocyte colony-stimulating factor therapy corrects the neutropenia and the defects in respiratory burst activity and Ca2. mobilization. Pediatr Res 35: 84–90.
Middleditch C, Clottes E, Burchell A (1998) A di¡erent isoform of the transport protein mutated in the glycogen storage disease 1b is expressed in brain. FEBS Lett 433: 33–36.
Miyamoto T, Nagafuji K, Akashi K, et al (1996) Persistence of mutipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21) acute myelogenous leukemia. Blood 87: 4789–4796.
Narisawa K, Igarashi Y, Otomo H, Tada K (1978) A new variant of glycogen storage disease type I probably due to a defect in the glucose-6-phosphate transport system. Biochem Biophys Res Commun 83: 1360–1364.
Schroten H, Roesler J, Breidenbach T, et al (1991) Granulocyte and granulocyte-macrophage colony-stimulating factors for treatment of neutropenia in glycogen storage disease type 1b. J Pediatr 119: 748–754.
Veiga-da-Cunha M, Gerin I, Chen YT, et al (1998) A gene on chromosome 11q23 coding for a putative glucose-6-phosphate translocase is mutated in glycogen-storage disease types 1b and 1c. Am J Hum Genet 63: 976–983.
Veiga-da-Cunha M, Gerin I, Chen YT, et al (1999) The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a. Eur J Hum Genet 7: 717–723.
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Ihara, K., Nomura, A., Hikino, S. et al. Quantitative analysis of glucose-6-phosphate translocase gene expression in various human tissues and haematopoietic progenitor cells. J Inherit Metab Dis 23, 583–592 (2000). https://doi.org/10.1023/A:1005677912539
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DOI: https://doi.org/10.1023/A:1005677912539