Location of Repository

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

By Bernard Burke, A. Pridmore, N. Harraghy, A. Collick, Jeremy Brown and Timothy J. Mitchell


Copyright © 2004, American Society for Microbiology. All Rights Reserved. Also available from http://cdli.asm.org/cgi/content/full/11/3/588We used the promoter of the human C-reactive protein (CRP) gene to drive inflammation-inducible overexpression\ud 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\ud GM-CSF within 6 h of intraperitoneal inoculation with 25 μg of lipopolysaccharide. However, some of the\ud 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

Publisher: American Society for Microbiology
Year: 2004
OAI identifier: oai:lra.le.ac.uk:2381/165

Suggested articles



  1. (1995). A STAT factor mediates the sexually dimorphic regulation of hepatic cytochrome P450 3A10/lithocholic acid 6-hydroxylase gene expression by growth hormone. doi
  2. (1999). Antimicrobial peptides as mediators of epithelial host defense. doi
  3. (2001). Bcl-2 mediates sex-specific differences in recovery of mice from LPS-induced signs of sickness independent of IL-6.
  4. (1980). Cytological studies of the developing vitreous as related to the hyaloid vessel system. Albrecht Graefes Arch. doi
  5. (1989). Developmental ocular disease in GM-CSF transgenic mice is mediated by autostimulated macrophages. doi
  6. (1999). Down-regulation of Liver JAK2-STAT5b signaling by the female plasma pattern of continuous growth hormone stimulation. doi
  7. (1989). Dual control of C-reactive protein gene-expression by interleukin-1 and interleukin-6.
  8. (1996). Estrogen inhibits interleukin-6 production and gene expression in a human osteoblastic cell line with high levels of estrogen receptors. doi
  9. (2001). Estrogen restores cellular immunity in injured male mice via suppression of interleukin-6 production. doi
  10. (1976). Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology 98:562–570. doi
  11. GM-CSF rapidly primes mice for enhanced cytokine production in response to LPS and TNF. doi
  12. GM-CSF-deficient mice are susceptible to pulmonary group B streptococcal infection. doi
  13. (1996). Granulocyte-macrophage colony stimulating factor (GM-CSF) enhances pulmonary defenses against pneumococcal infections after splenectomy. doi
  14. (1996). Granulocyte-macrophage colony-stimulating factor and the immune system. doi
  15. (1999). Granulocyte-macrophage colony-stimulating factor modulates lipopolysaccharide (LPS)-binding and LPS-response of human macrophages: inverse regulation of tumour necrosis factor-alpha and interleukin-10. Immunology 98:491–496. doi
  16. (1996). Granulocytemacrophage colony-stimulating factor: involvement in control of Trypanosoma cruzi infection in mice.
  17. (1995). Human C-reactive protein is protective against fatal Streptococcus pneumoniae infection in transgenic mice.
  18. (1988). Identification of sequences responsible for acute-phase induction of human C-reactive protein. Nucleic Acids Res. doi
  19. (1987). Inducible and tissue-specific expression of human C-reactive protein in transgenic mice. doi
  20. Interaction of STAT5 dimers on two low-affinity binding sites mediates interleukin-2 (IL-2) stimulation of IL-2 receptor gene transcription. doi
  21. (1993). Male-specific expression of mouse sex-limited protein requires growth-hormone, not testosterone. doi
  22. (1998). Male-specific transcription of the C4-Slp gene in mouse liver follows activation of STAT5. doi
  23. (1999). Mechanisms of disease: acute-phase proteins and other systemic responses to inflammation. doi
  24. (1989). Protective effect of recombinant murine granulocyte-macrophage colony-stimulating factor against Pseudomonas aeruginosa infection in leukocytopenic mice.
  25. (1995). Regulation of the human C-reactive protein gene in transgenic mice. doi
  26. (1987). Sexually dimorphic patterns of growth hormone secretion.
  27. (1997). STAT5a-deficient mice demonstrate a defect in granulocyte-macrophage colonystimulating factor-induced proliferation and gene expression.
  28. (1998). Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice.
  29. (1990). The ability of recombinant murine granulocyte-macrophage colony-stimulating factor to protect neonatal rats from septic death due to Staphylococcus aureus. doi
  30. (1995). The effect of interleukin-1 on C-reactive protein expression in Hep3B cells is exerted at the transcriptional level. doi
  31. (2000). The role of STAT proteins in growth hormone signaling. Oncogene 19:2585–2597. doi
  32. (1987). Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage. doi
  33. (1993). Transgenic mice in the study of cytokine function. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.