From Classical Mouse Models of Psoriasis to a Spontaneous Xenograft Model Featuring Use of AGR Mice

  • F. O. Nestle
  • B. J. Nickoloff
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 50)

11.6 Conclusions

Psoriasis is one of the most prevalent T cell-mediated chronic inflammatory diseases. However, there is still a poor understanding of this disease’s pathogenesis, as well as an array of therapeutic agents with ill-defined mechanisms of action. Newer xenotransplantation mouse models such as the AGR129 mouse model hopefully will provide the necessary scientific insights to connect new therapeutic measures such as biological agents with disease pathogenesis in this enigmatic disease.


SCID Mouse Knockout Mouse Model Inflammatory Skin Disease Transform Growth Factor Alpha Epidermal Hyperplasia 
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  1. Arundell FD, Karasek MA, Gates AH (1969) 7,12-dimethylbenzanthracene tumor induction in mutant (hairless, asebic, and hairless-asebic) mice. J Invest Dermatol 52:119–125PubMedGoogle Scholar
  2. Ashcroft DM, Wan Po AL, Williams HC, Griffiths CE (1999) Clinical measures of disease severity and outcome in psoriasis: a critical appraisal of their quality. Br J Dermatol 141:185–191PubMedCrossRefGoogle Scholar
  3. Boyman O, Hefti HP, Conrad C, Nickoloff BJ, Suter M, Nestle FO (2004) Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-α. J Exp Med 199:731–736PubMedCrossRefGoogle Scholar
  4. Bullard DC, Scharffetter-Kochanek K, McArthur MJ, Chosay JG, McBride ME, Montgomery CA, Beaudet AL (1996) A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice. Proc Natl Acad Sci 93:2116–2121PubMedCrossRefGoogle Scholar
  5. Carroll JM, Romero MR, Watt FM (1995) Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis. Cell 83:957–968PubMedCrossRefGoogle Scholar
  6. Carroll JM, Crompton T, Seery JP, Watt FM (1997) Transgenic mice expressing IFN-γ in the epidermis have eczema, hair hypopigmentation, and hair loss. J Invest Dermatol 108:412–422PubMedCrossRefGoogle Scholar
  7. Chen CL, Yull FE, Cardwell N, Singh N, Strayhorn WD, Nanney LB, Kerr LD (2000) RAG2-/-, IκB-α-/-chimeras display a psoriasiform skin disease. J Invest Dermatol 115:1124–1133PubMedCrossRefGoogle Scholar
  8. Cook PW, Piepkorn M, Clegg CH, Plowman GD, DeMay JM, Brown JR, Pittelkow MR (1997) Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype. J Clin Invest 100:2286–2294PubMedCrossRefGoogle Scholar
  9. Dam TN, Kang S, Nickoloff BJ, Voorhees JJ (1999) 1α,25-dihydroxychole-calciferol and cyclosporine suppress induction and promote resolution of psoriasis in human skin grafts transplanted on to SCID mice. J Invest Dermatol 113:1082–1089PubMedCrossRefGoogle Scholar
  10. Detmar M, Brown LF, Schon MP, Elicker BM, Velasco P, Richard L, Fukumura D, Monsky W, Claffey KP, Jain RK (1998) Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J Invest Dermatol 111:1–6PubMedCrossRefGoogle Scholar
  11. Fraki JE, Briggaman RA, Lazarus GS (1983) Transplantation of psoriatic skin onto nude mice. J Invest Dermatol 80(Suppl):31s–35sPubMedCrossRefGoogle Scholar
  12. Grob P, Schijns VE, van den Broek MF, Cox SP, Ackermann M, Suter M (1999) Role of the individual interferon systems and specific immunity in mice in controlling systemic dissemination of attenuated pseudorabies virus infection. J Virol 73:4748–4754PubMedGoogle Scholar
  13. Groves RW, Mizutani H, Kieffer JD, Kupper TS (1995) Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 α in basal epidermis. Proc Natl Acad Sci 92:11874–11878PubMedCrossRefGoogle Scholar
  14. Guo L, Yu QC, Fuchs E (1993) Targeting expression of keratinocyte growth factor to keratinocytes elicits striking changes in epithelial differentiation in transgenic mice. EMBO J 12:973–986PubMedGoogle Scholar
  15. Krueger JG (2002) The immunologic basis for the treatment of psoriasis with new biologic agents. J Am Acad Dermatol 46:1–23; quiz 23–26PubMedCrossRefGoogle Scholar
  16. Kupper TS (1989) Production of cytokines by epithelial tissues. A new model for cutaneous inflammation. Am J Dermatopathol 11:69–73PubMedCrossRefGoogle Scholar
  17. Nickoloff BJ (1991) The cytokine network in psoriasis. Arch Dermatol 127:871–884PubMedCrossRefGoogle Scholar
  18. Pasparakis M, Courtois G, Hafner M, Schmidt-Supprian M, Nenci A, Toksoy A, Krampert M, Goebeler M, Gillitzer R, Israel A, Krieg T, Rajewsky K, Haase I (2002) TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature 417:861–866PubMedCrossRefGoogle Scholar
  19. Schon MP (1999) Animal models of psoriasis — what can we learn from them? J Invest Dermatol 112:405–410PubMedCrossRefGoogle Scholar
  20. Seitz CS, Lin Q, Deng H, Khavari PA (1998) Alterations in NF-κB function in transgenic epithelial tissue demonstrate a growth inhibitory role for NF-κB. Proc Natl Acad Sci 95:2307–2312PubMedCrossRefGoogle Scholar
  21. Sundberg JP, France M, Boggess D, Sundberg BA, Jenson AB, Beamer WG, Shultz LD (1997) Development and progression of psoriasiform dermatitis and systemic lesions in the flaky skin (fsn) mouse mutant. Pathobiology 65:271–286PubMedCrossRefGoogle Scholar
  22. Turksen K, Kupper T, Degenstein L, Williams I, Fuchs E (1992) Interleukin 6: insights to its function in skin by overexpression in transgenic mice. Proc Natl Acad Sci 89:5068–5072PubMedCrossRefGoogle Scholar
  23. Vassar R, Fuchs E (1991) Transgenic mice provide new insights into the role of TGF-α during epidermal development and differentiation. Genes Dev 5:714–727PubMedCrossRefGoogle Scholar
  24. Wrone-Smith T, Nickoloff BJ (1996) Dermal injection of immunocytes induces psoriasis. J Clin Invest 98:1878–1887PubMedCrossRefGoogle Scholar
  25. Xia YP, Li B, Hylton D, Detmar M, Yancopoulos GD, Rudge JS (2003) Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis. Blood 102:161–168PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • F. O. Nestle
    • 1
  • B. J. Nickoloff
    • 2
  1. 1.Department of Dermatology, Medical SchoolUniversity of ZurichZürichSwitzerland
  2. 2.Department of Pathology, Oncology InstituteLoyola University Medical CenterChicagoUSA

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