Transgenic mice showing inflammation-inducible overexpression of granulocyte macrophage colony-stimulating factor

B Burke, A Pridmore, N Harraghy, A Collick, Jane Brown, T Mitchell

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    12 Citations (Scopus)

    Abstract

    We used the promoter of the human C-reactive protein (CRP) gene to drive inflammation-inducible overexpression of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in transgenic mice. Transgenic mice carrying a CRP/GM-CSF fusion gene show a >150-fold increases in circulating levels of GM-CSF within 6 h of intraperitoneal inoculation with 25 microg of lipopolysaccharide. However, some of the transgenic mice also display relatively high basal levels of GM-CSF in the absence of any obvious inflammatory stimulus. Raised basal levels of GM-CSF are associated with a number of pathological changes, including enlarged and histologically abnormal livers and spleens and with increases in the number and activation state of macrophages and granulocytes in the peripheral blood. Despite problems associated with the expression of such a potent pleiotropic cytokine as GM-CSF, the principle of inflammation-inducible expression of chimeric constructs has been shown to be feasible. Inducible expression systems such as that described here could be of potential use in the study of the role of cytokines in health and disease and in the development of disease-resistant strains of livestock.

    Original languageEnglish
    Pages (from-to)588-598
    Number of pages11
    JournalClinical and Diagnostic Laboratory Immunology
    Volume11
    Issue number3
    DOIs
    Publication statusPublished - May 2004

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    Keywords

    • Amino Acid Sequence
    • Animals
    • Base Sequence
    • Binding Sites/genetics
    • C-Reactive Protein/genetics
    • Cell Line, Tumor
    • DNA-Binding Proteins/genetics
    • Female
    • Flow Cytometry
    • Gene Expression Regulation/drug effects
    • Genetic Vectors/genetics
    • Granulocyte-Macrophage Colony-Stimulating Factor/blood
    • Humans
    • Inflammation/genetics
    • Interleukin-1/pharmacology
    • Interleukin-6/blood
    • Leukocyte Count
    • Lipopolysaccharides/pharmacology
    • Macrophages/cytology
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Mice, Inbred CBA
    • Mice, Transgenic
    • Milk Proteins/genetics
    • Molecular Sequence Data
    • Neutrophils/cytology
    • Peritoneal Cavity/cytology
    • Polymerase Chain Reaction
    • Promoter Regions, Genetic/genetics
    • Recombinant Fusion Proteins/genetics
    • STAT5 Transcription Factor
    • Sex Factors
    • Spleen/cytology
    • Trans-Activators/genetics
    • Transfection

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