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Clinical and Diagnostic Laboratory Immunology, May 2004, p. 588-598, Vol. 11, No. 3
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.3.588-598.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Transgenic Mice Showing Inflammation-Inducible Overexpression of Granulocyte Macrophage Colony-Stimulating Factor

B. Burke,^1, A. Pridmore,^1, N. Harraghy,^1, A. Collick,² J. Brown,³ and T. Mitchell^1*

Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ,¹ MRC Toxicology Unit,² Biomedical Sciences Unit, University of Leicester, Leicester LE1-9HN, United Kingdom³

Received 16 October 2003/ Returned for modification 29 December 2003/ Accepted 22 January 2004

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 µg 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.

Present address: Department of Infection, Immunity, and Inflammation, Medical Sciences Building, University of Leicester, Leicester, United Kingdom.

Present address: Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom.

Present address: Institute of Medical Microbiology and Hygiene, University of Saarland, D-66421 Homburg/Saar, Germany.

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