Genetic factors in animal models of intestinal inflammation

  • R. B. Sartor

Abstract

Clinical investigators have compellingly documented a genetic component in ulcerative colitis and Crohn’s disease1. There is an increased incidence of inflammatory bowel disease (IBD) in family members, a predilection for these disorders in certain genetically defined ethnic groups, higher concordance of disease in monozygotic versus dizygotic twins, and familial patterns of clinical phenotypes. However, human genetic research has not yet provided clinically useful disease susceptibility markers, or an understanding of the immunopathogenesis of IBD.

Keywords

Inflammatory Bowel Disease Ulcerative Colitis Inflammatory Bowel Disease Patient Intestinal Inflammation Human Inflammatory Bowel Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Yang H, Rotter JI. Subclinical markers of human IBD. In Sutherland LR, Collins SM, Martin F, et al, editors. Inflammatory bowel disease: basic research, clinical implications and trends in therapy. Lancaster: Kluwer Academic Publishers; 1994: chap 1.Google Scholar
  2. 2.
    Lushbaugh C, Humason G, Clapp N. Histology of colitis: Saguinus oedipus and other marmosets. Dig Dis Sci. 1985; 30: 45–51S.CrossRefGoogle Scholar
  3. 3.
    Chalifoux IV, Brieland JK, King KW. Evolution and natural history of colonic disease in cotton-top tamarins (Saguinus oedipus). Dig Dis Sci. 1985; 30: 54–8S.CrossRefGoogle Scholar
  4. 4.
    Madara JL, Podolsky DK, King NW, Sehgal PK, Moore R, Winter HS. Characterization of spontaneous colitis in cotton-top tamarins (Saguinus oedipus) and its response to sulfasalazine. Gastroenterology. 1985; 88: 13–19.PubMedGoogle Scholar
  5. 5.
    Sartor RB. Animal models of intestinal inflammation: relevance to IBD. In: MacDermott RP, Stenson W, editors. Inflammatory bowel disease. New York: Elsevier; 1991: 337–54.Google Scholar
  6. 6.
    Podolsky DK, Madara JL, King N et al. Colonic mucin composition in primates. Gastroenterology. 1985; 88: 20–5.PubMedGoogle Scholar
  7. 7.
    Targan SR, Landers CJ, King NW, Podolsky DJ, Shanahan F. Ulcerative colitis-linked antineutrophil cytoplasmic antibody in the cotton-top tamarin model of colitis. Gastroenterology. 1992; 102: 1493–8.PubMedGoogle Scholar
  8. 8.
    Winter HS, Crum PM Jr, King NW, Sehgal PK, Roche JK. Expression of immune sensitization to epithelial cell-associated components in the cotton-top tamarin: a model of chronic ulcerative colitis. Gastroenterology. 1989; 97: 1075–82.PubMedGoogle Scholar
  9. 9.
    Birkenmeier EH, Sundberg JP, Elson CO. A heritable form of colitis in mice. Gastroenterology. 1991; 102: A596.Google Scholar
  10. 10.
    McCabe RP, Mills T, Ridwan B et al. Immunologic reactivity in C3H/HeJ mice with spontaneous colitis. Gastroenterology. 1993; 104: A739.Google Scholar
  11. 11.
    Brandwein SL, McCabe RP, Dadrat A et al. Immunologic reactivity of colitic C3H/HeJ Bir mice to enteric bacteria. Gastroenterology. 1994; 106: A656.Google Scholar
  12. 12.
    Sadlack B, Merg H, Schorle H et al. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell. 1993; 75: 253–61.PubMedCrossRefGoogle Scholar
  13. 13.
    Kuhn R, Lohler J, Rennick D, Rajowsky K, Muller W. Interleukin-1-deficient mice develop chronic enterocolitis. Cell. 1993; 75: 263–79.PubMedCrossRefGoogle Scholar
  14. 14.
    Kulkarni AB, Huh CG, Becker D et al. Transforming growth factor ßl null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci. 1993; 90: 770–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Mombaerts P, Mizoguchi E, Grusby M et al. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell. 1993; 75: 275–82.CrossRefGoogle Scholar
  16. 16.
    Hammer RE, Maika SD, Richardson JA, Tang J, Taurog JD. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: an animal model of HLAB27-associated human disorders. Cell. 1990; 63: 1099–112.PubMedCrossRefGoogle Scholar
  17. 17.
    Taurog JD, Maika SD, Simmons WA, Breban M, Hammer RE. Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression. J Immunol. 1993; 150: 4186.Google Scholar
  18. 18.
    Breban M, Hammer RE, Richardson JA, Taurog JD. Transfer of the inflammatory disease of HLA-B27 transgenic rats by bone marrow engraftment. J Exp Med. 1993; 178: 1607–16.PubMedCrossRefGoogle Scholar
  19. 19.
    Taurog JD, Hammer RE, Balish E et al. Effect of the germfree state on the inflammatory disease of HLA-B27 transgenic rats: a split result. Arthritis Rheum. 1993; 36: S46.Google Scholar
  20. 20.
    McCall RD, Haskill S, Zimmerman E et al. Tissue IL-1 and IL-1 receptor antagonist expression in enterocolitis in resistant and susceptible rats. Gastroenterology. 1994; 106: 960–72.PubMedGoogle Scholar
  21. 21.
    Sartor RB, Cromartie WH, Powell DW et al. Granulomatous enterocolitis induced in rats by purified bacterial cell wall fragments. Gastroenterology. 1985; 89: 587–95.PubMedGoogle Scholar
  22. 22.
    Sartor RB, Bender DE, Holt LC. Susceptibility of inbred rat strains to intestinal and extraintestinal inflammation induced by indomethacin. Gastroenterology. 1992; 102: A690.Google Scholar
  23. 23.
    Lichtman SN, Sartor RB, Schwab JH, Keku J. Hepatic inflammation in rats with experimental small bowel bacterial overgrowth. Gastroenterology. 1990; 98: 414–23.PubMedGoogle Scholar
  24. 24.
    Moore MJ, Singer DE, William RM. Linkage of severity of experimental allergic encephalomyelitis to the rat major histocompatibility locus. J Immunol. 1980; 124: 1815–20.PubMedGoogle Scholar
  25. 25.
    Schwab JH. Phlogistic properties of peptidoglycan-polysaccharide polymers from cell walls of pathogenic and normal-flora bacteria which colonize humans. Infect Immun. 1993; 61: 4535–9.PubMedGoogle Scholar
  26. 26.
    Sternberg EM, Hill JM, Chrousos GP et al. Inflammatory mediator-induced hypothalamicpituitary-adrenal activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc Natl Acad Sci USA. 1989; 86: 2374–8.PubMedCrossRefGoogle Scholar
  27. 27.
    McCall RD, Haskill JS, Sartor RB. Constitutive expression of TNFa and of an IL-8 like gene is associated with genetic susceptibility to chronic granulomatous enterocolitis in inbred rats. Gastroenterology. 1993; 104: A740.Google Scholar
  28. 28.
    Sartor RB, Bender DE, Allen JB et al. Chronic experimental enterocolitis and extraintestinal inflammation are T lymphocyte dependent. Gastroenterology. 1993; 104: 775A.Google Scholar
  29. 29.
    Bristol LA, Durum SK, Eisenberg SP. Differential regulation of group A streptococcal peptidoglycan-polysaccharide (PG-APS)-stimulated macrophage production of IL-1 by rat strains susceptible and resistant to PG-APS-induced arthritis. Cell Immunol. 1993; 149: 130–43.PubMedCrossRefGoogle Scholar
  30. 30.
    Isaacs KL, Sartor RB, Haskill JS. Cytokine mRNA profiles in inflammatory bowel disease mucosa detected by PCR amplification. Gastroenterology. 1992; 103: 1587–95.PubMedGoogle Scholar
  31. 31.
    Isaacs KL, Sartor RB, Haskill JS. Relative expression of IL-1 and IL-1 receptor antagonist in IBD. Gastroenterology. 1992; 102: A729.Google Scholar
  32. 32.
    Beagley KW, Black DA, Elson CO. Strain differences in susceptibility to TNBS-induced colitis. Gastroenterology. 1991; 100: A560.Google Scholar
  33. 33.
    Barthold SW, Osbaldiston GW, Jonas AM. Dietary, bacterial, and host genetic interactions in the pathogenesis of transmissible murine colonic hyperplasia. Lab Anim Sci. 1977; 27: 938–45.PubMedGoogle Scholar
  34. 34.
    Sartor RB. Role of the intestinal microflora in the pathogenesis and complications. In: Scholmerik J, Kruis W, Goebel H, Hohenberger W, Gross V, editors. Inflammatory bowel diseases: pathology as basis of treatment. Falk Symposium 67. Dordrecht: Kluwer; 1993: 175–87.Google Scholar

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© Kluwer Academic Publishers and Axcan Pharma, Inc. 1994

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  • R. B. Sartor

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