Transgenic mice showing inflammation-inducible overexpression of granulocyte macrophage colony-stimulating factor.
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.
Burke
B
B
Division of Infection and Immunity, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Pridmore
A
A
Harraghy
N
N
Collick
A
A
Brown
J
J
Mitchell
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002097:C-Reactive Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood / Q000494:pharmacology; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology; D010529:Peritoneal Cavity / Q000166:cytology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor; D012737:Sex Factors; D013154:Spleen / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics; D014162:Transfection
D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008894:Milk Proteins; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein