Skip NavigationSkip to Content
Return Return to Search Results

Impaired glucose homeostasis, neutrophil trafficking and function in mice lacking the glucose-6-phosphate transporter

  1. Author:
    Chen, L. Y.
    Shieh, J. J.
    Lin, B. C.
    Pan, C. J.
    Gao, J. L.
    Murphy, P. M.
    Roe, T. F.
    Moses, S.
    Ward, J. M.
    Lee, E. J.
    Westphal, H.
    Mansfield, B. C.
    Chou, J. Y.

  2. Author Address

    NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Room 9S241, Bethesda, MD 20892 USA NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA Univ So Calif, Sch Med, Dept Pediat, Los Angeles, CA 90027 USA Ben Gurion Univ Negev, Div Pediat, IL-84105 Beer Sheva, Israel NCI, Vet & Tumor Pathol Sect, Off Lab Anim Sci, Frederick, MD 21702 USA Chou JY NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Room 9S241, Bethesda, MD 20892 USA
    1. Year: 2003
  2. Journal: Human Molecular Genetics
    1. 12
    2. 19
    3. Pages: 2547-2558
  4. Type of Article: Article
  1. Abstract:

    Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate transporter (G6PT). In addition to disrupted glucose homeostasis, GSD-Ib patients have unexplained and unexpected defects in neutrophil respiratory burst, chemotaxis and calcium flux, in response to the bacterial peptide f-Met-Leu-Phe, as well as intermittent neutropenia. We generated a G6PT knockout (G6PT(-/-)) mouse that mimics all known defects of the human disorder and used the model to further our understanding of the pathogenesis of GSD-Ib. We demonstrate that the neutropenia is caused directly by the loss of G6PT activity; that chemotaxis and calcium flux, induced by the chemokines KC and macrophage inflammatory protein-2, are defective in G6PT(-/-) neutrophils; and that local production of these chemokines and the resultant neutrophil trafficking in vivo are depressed in G6PT(-/-) ascites during an inflammatory response. The bone and spleen of G6PT(-/-) mice are developmentally delayed and accompanied by marked hypocellularity of the bone marrow, elevation of myeloid progenitor cell frequencies in both organs and a corresponding dramatic increase in granulocyte colony stimulating factor levels in both GSD-Ib mice and humans. So, in addition to transient neutropenia, a sustained defect in neutrophil trafficking due to both the resistance of neutrophils to chemotactic factors, and reduced local production of neutrophil-specific chemokines at sites of inflammation, may underlie the myeloid deficiency in GSD-Ib. These findings demonstrate that G6PT is not just a G6P transport protein but also an important immunomodulatory protein whose activities need to be addressed in treating the myeloid complications in GSD-Ib patients.

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel