Animal Models for the Biological Effects of Continuous High Cytokine Levels

Overview

Journal Blut

Specialty Hematology

Date 1990 Nov 1

PMID 2271771

Authors

M Lubbert

D Jonas

F Herrmann

Affiliations

Soon will be listed here.

Abstract

Transgenic animals or animals engrafted with retrovirus-derived expression vectors provide models for studying the in vivo effects of high and continuous serum levels of cytokines. Studies employing these models in order to analyze the biological effects for granulocytes-macrophages colony-stimulating factors (CSFs), granulocytes of interleukin (IL-)2, IL-3, IL-6 and erythropoietin are reviewed. In all of these models, overexpression of the different cytokines achieved by use of these approaches resulted in syndromes that were related to nonneoplastic hyperplasia of the respective target cell population. In some but not all models, these syndromes were lethal, mostly due to hypercellularity. These models allow conclusions about the biological effects of very high and continuous levels of these substances as well as about their regulation in different tissues.

References

Brinster R, Chen H, Trumbauer M, Yagle M, Palmiter R . Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc Natl Acad Sci U S A. 1985; 82(13):4438-42. PMC: 391116. DOI: 10.1073/pnas.82.13.4438. View

Kishimoto T, Hirano T . Molecular regulation of B lymphocyte response. Annu Rev Immunol. 1988; 6:485-512. DOI: 10.1146/annurev.iy.06.040188.002413. View

Herrmann F, Lindemann A, Mertelsmann R . Polypeptides controlling hematopoietic blood cell development and activation. II. Clinical results. Blut. 1989; 58(4):173-9. DOI: 10.1007/BF00320769. View

Lang R, Metcalf D, Cuthbertson R, Lyons I, Stanley E, Kelso A . Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage. Cell. 1987; 51(4):675-86. DOI: 10.1016/0092-8674(87)90136-x. View

Wong P, Chung S, Dunbar C, Bodine D, Ruscetti S, Nienhuis A . Retrovirus-mediated transfer and expression of the interleukin-3 gene in mouse hematopoietic cells result in a myeloproliferative disorder. Mol Cell Biol. 1989; 9(2):798-808. PMC: 362657. DOI: 10.1128/mcb.9.2.798-808.1989. View

Spooncer E, Katsuno M, Hampson I, Dexter T, Just U, Stocking C . Biological effects of retroviral transfection of the murine interleukin-3 gene into FDCP-Mix cells. Curr Top Microbiol Immunol. 1989; 149:109-16. DOI: 10.1007/978-3-642-74623-9_10. View

Gearing A, Metcalf D, Moore J, Nicola N . Elevated levels of GM-CSF and IL-1 in the serum, peritoneal and pleural cavities of GM-CSF transgenic mice. Immunology. 1989; 67(2):216-20. PMC: 1385260. View

Ishida Y, Nishi M, Taguchi O, Inaba K, Minato N, Kawaichi M . Effects of the deregulated expression of human interleukin-2 in transgenic mice. Int Immunol. 1989; 1(2):113-20. DOI: 10.1093/intimm/1.2.113. View

Johnson G, Gonda T, Metcalf D, Hariharan I, Cory S . A lethal myeloproliferative syndrome in mice transplanted with bone marrow cells infected with a retrovirus expressing granulocyte-macrophage colony stimulating factor. EMBO J. 1989; 8(2):441-8. PMC: 400825. DOI: 10.1002/j.1460-2075.1989.tb03396.x. View

10.

Semenza G, Dureza R, Traystman M, Gearhart J, Antonarakis S . Human erythropoietin gene expression in transgenic mice: multiple transcription initiation sites and cis-acting regulatory elements. Mol Cell Biol. 1990; 10(3):930-8. PMC: 360936. DOI: 10.1128/mcb.10.3.930-938.1990. View

11.

Chang J, Metcalf D, Gonda T, Johnson G . Long-term exposure to retrovirally expressed granulocyte-colony-stimulating factor induces a nonneoplastic granulocytic and progenitor cell hyperplasia without tissue damage in mice. J Clin Invest. 1989; 84(5):1488-96. PMC: 304013. DOI: 10.1172/JCI114324. View

12.

Ishida Y, Nishi M, Taguchi O, Inaba K, Hattori M, Minato N . Expansion of natural killer cells but not T cells in human interleukin 2/interleukin 2 receptor (Tac) transgenic mice. J Exp Med. 1989; 170(4):1103-15. PMC: 2189472. DOI: 10.1084/jem.170.4.1103. View

13.

Horii Y, Muraguchi A, Iwano M, Matsuda T, Hirayama T, Yamada H . Involvement of IL-6 in mesangial proliferative glomerulonephritis. J Immunol. 1989; 143(12):3949-55. View

14.

Nishi M, Ishida Y, Honjo T . Expression of functional interleukin-2 receptors in human light chain/Tac transgenic mice. Nature. 1988; 331(6153):267-9. DOI: 10.1038/331267a0. View

15.

Tani K, Ozawa K, Ogura H, Takahashi T, Okano A, Watari K . Implantation of fibroblasts transfected with human granulocyte colony-stimulating factor cDNA into mice as a model of cytokine-supplement gene therapy. Blood. 1989; 74(4):1274-80. View

16.

Harbers K, Jahner D, Jaenisch R . Microinjection of cloned retroviral genomes into mouse zygotes: integration and expression in the animal. Nature. 1981; 293(5833):540-2. DOI: 10.1038/293540a0. View

17.

Suematsu S, Matsuda T, Aozasa K, Akira S, Nakano N, Ohno S . IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1989; 86(19):7547-51. PMC: 298102. DOI: 10.1073/pnas.86.19.7547. View

18.

Semenza G, Traystman M, Gearhart J, Antonarakis S . Polycythemia in transgenic mice expressing the human erythropoietin gene. Proc Natl Acad Sci U S A. 1989; 86(7):2301-5. PMC: 286900. DOI: 10.1073/pnas.86.7.2301. View

19.

Sporn M, Roberts A . Autocrine growth factors and cancer. Nature. 1985; 313(6005):745-7. DOI: 10.1038/313745a0. View

20.

Clark S, Kamen R . The human hematopoietic colony-stimulating factors. Science. 1987; 236(4806):1229-37. DOI: 10.1126/science.3296190. View