Skip to main content
SpringerLink
Log in

Mouse Models of Chronic Intestinal Inflammation: Characterization and Use in Pharmacological Intervention Studies

  • Chapter
  • First Online:
Crohn's Disease and Ulcerative Colitis

  • 3509 Accesses

Abstract

Mouse models of disease have been used extensively by the research community for the past three decades to better understand the pathogenesis of different diseases as well as to assess the efficacy and toxicity of different therapeutic agents. Retrospective analyses of numerous preclinical intervention studies using mouse models of acute and chronic inflammatory diseases reveal a generalized failure to translate promising interventions or therapeutics into clinically effective treatments in patients. This is especially true for preclinical investigations using mouse models of the inflammatory bowel diseases (IBD; Crohn’s disease, ulcerative colitis). One potential strategy for improving our ability to discover new therapeutics that may have a reasonable chance of success in clinical trials is to identify the most immunologically-relevant mouse models of human IBD. However, it is becoming increasingly appreciated that the mouse immune system differs substantially from that of humans, and thus, may not express the same pathogenetic mechanisms that are thought to occur in human IBD. This chapter presents a critical evaluation of selected mouse models of IBD and discusses their utility in preclinical studies. In addition, we describe recent advances in generating and utilizing “humanized” mice to study the pathogenesis and treatment of chronic gut inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Koboziev I, Karlsson F, Zhang S, Grisham MB. Pharmacological intervention studies using mouse models of the inflammatory bowel diseases: translating preclinical data into new drug therapies. Inflamm Bowel Dis. 2011;17(5):1229–45.

    Article  PubMed  PubMed Central  Google Scholar 

  2. DeVoss J, Diehl L. Murine models of inflammatory bowel disease (IBD): challenges of modeling human disease. Toxicol Pathol. 2014;42(1):99–110.

    Article  PubMed  Google Scholar 

  3. Hackam DG, Redelmeier DA. Translation of research evidence from animals to humans. JAMA. 2006;296(14):1731–2.

    Article  CAS  PubMed  Google Scholar 

  4. Hackam DG. Translating animal research into clinical benefit. BMJ. 2007;334(7586):163–4.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sena ES, van der Worp HB, Bath PM, Howells DW, Macleod MR. Publication bias in reports of animal stroke studies leads to major overstatement of efficacy. PLoS Biol. 2010;8(3), e1000344.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Sena ES, Currie GL, McCann SK, Macleod MR, Howells DW. Systematic reviews and meta-analysis of preclinical studies: why perform them and how to appraise them critically. J Cereb Blood Flow Metab. 2014;34(5):737–42.

    Article  PubMed  PubMed Central  Google Scholar 

  7. van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, O'Collins V, et al. Can animal models of disease reliably inform human studies? PLoS Med. 2010;7(3), e1000245.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Valatas V, Vakas M, Kolios G. The value of experimental models of colitis in predicting efficacy of biological therapies for inflammatory bowel diseases. Am J Physiol Gastrointest Liver Physiol. 2013;305(11):G763–85.

    Article  CAS  PubMed  Google Scholar 

  9. Elson CO, Cong Y, McCracken VJ, Dimmitt RA, Lorenz RG, Weaver CT. Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol Rev. 2005;206:260–76.

    Article  PubMed  Google Scholar 

  10. Maxwell JR, Viney JL. Overview of mouse models of inflammatory bowel disease and their use in drug discovery. Curr Protoc Pharmacol. 2009;47:5.57.1–19.

    Google Scholar 

  11. Strober W, Fuss IJ, Blumberg RS. The immunology of mucosal models of inflammation. Annu Rev Immunol. 2002;20:495–549.

    Article  CAS  PubMed  Google Scholar 

  12. Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007;117(3):514–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Uhlig HH, Powrie F. Mouse models of intestinal inflammation as tools to understand the pathogenesis of inflammatory bowel disease. Eur J Immunol. 2009;39(8):2021–6.

    Article  CAS  PubMed  Google Scholar 

  14. Cho JH, Weaver CT. The genetics of inflammatory bowel disease. Gastroenterology. 2007;133(4):1327–39.

    Article  CAS  PubMed  Google Scholar 

  15. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448(7152):427–34.

    Article  CAS  PubMed  Google Scholar 

  16. Jones-Hall YL, Grisham MB. Immunopathological characterization of selected mouse models of inflammatory bowel disease: comparison to human disease. Pathophysiology. 2014;21(4):267–88.

    Article  PubMed  Google Scholar 

  17. Chidlow Jr JH, Langston W, Greer JJ, Ostanin D, Abdelbaqi M, Houghton J, et al. Differential angiogenic regulation of experimental colitis. Am J Pathol. 2006;169(6):2014–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Siegmund B, Lehr HA, Fantuzzi G. Leptin: a pivotal mediator of intestinal inflammation in mice. Gastroenterology. 2002;122(7):2011–25.

    Article  CAS  PubMed  Google Scholar 

  19. Siegmund B, Sennello JA, Lehr HA, Batra A, Fedke I, Zeitz M, et al. Development of intestinal inflammation in double IL-10- and leptin-deficient mice. J Leukoc Biol. 2004;76(4):782–6.

    Article  CAS  PubMed  Google Scholar 

  20. Te Velde AA, de KF, Sterrenburg E, Pronk I, ten Kate FJ, Hommes DW, et al. Comparative analysis of colonic gene expression of three experimental colitis models mimicking inflammatory bowel disease. Inflamm Bowel Dis. 2007;13(3):325–30.

    Article  Google Scholar 

  21. Vowinkel T, Anthoni C, Wood KC, Stokes KY, Russell J, Gray L, et al. CD40-CD40 ligand mediates the recruitment of leukocytes and platelets in the inflamed murine colon. Gastroenterology. 2007;132(3):955–65.

    Article  CAS  PubMed  Google Scholar 

  22. Hawkey CJ, Dube LM, Rountree LV, Linnen PJ, Lancaster JF. A trial of zileuton versus mesalazine or placebo in the maintenance of remission of ulcerative colitis. The European Zileuton Study Group For Ulcerative Colitis. Gastroenterology. 1997;112(3):718–24.

    Article  CAS  PubMed  Google Scholar 

  23. Roberts WG, Simon TJ, Berlin RG, Haggitt RC, Snyder ES, Stenson WF, et al. Leukotrienes in ulcerative colitis: results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591. Gastroenterology. 1997;112(3):725–32.

    Article  CAS  PubMed  Google Scholar 

  24. Dieleman LA, Ridwan BU, Tennyson GS, Beagley KW, Bucy RP, Elson CO. Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice. Gastroenterology. 1994;107(6):1643–52.

    Article  CAS  PubMed  Google Scholar 

  25. Fiorucci S, Mencarelli A, Palazzetti B, Sprague AG, Distrutti E, Morelli A, et al. Importance of innate immunity and collagen binding integrin alpha1beta1 in TNBS-induced colitis. Immunity. 2002;17(6):769–80.

    Article  CAS  PubMed  Google Scholar 

  26. Nguyen LP, Pan J, Dinh TT, Hadeiba H, O'Hara III E, Ebtikar A, et al. Role and species-specific expression of colon T cell homing receptor GPR15 in colitis. Nat Immunol. 2015;16(2):207–13.

    Article  CAS  PubMed  Google Scholar 

  27. Soriano A, Salas A, Salas A, Sans M, Gironella M, Elena M, et al. VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice. Lab Invest. 2000;80(10):1541–51.

    Article  CAS  PubMed  Google Scholar 

  28. Wang C, Hanly EK, Wheeler LW, Kaur M, McDonald KG, Newberry RD. Effect of alpha4beta7 blockade on intestinal lymphocyte subsets and lymphoid tissue development. Inflamm Bowel Dis. 2010;16(10):1751–62.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Rongvaux A, Takizawa H, Strowig T, Willinger T, Eynon EE, Flavell RA, et al. Human hemato-lymphoid system mice: current use and future potential for medicine. Annu Rev Immunol. 2013;31:635–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Receptive to replication. Nat Biotechnol 2013;31(11):943.

    Google Scholar 

  31. Arrowsmith J. Trial watch: phase II failures: 2008–2010. Nat Rev Drug Discov. 2011;10(5):328–9.

    Article  CAS  PubMed  Google Scholar 

  32. Begley CG, Ellis LM. Drug development: raise standards for preclinical cancer research. Nature. 2012;483(7391):531–3.

    Article  CAS  PubMed  Google Scholar 

  33. Couzin-Frankel J. When mice mislead. Science. 2013;342(6161):922–3. 925.

    Article  CAS  PubMed  Google Scholar 

  34. Prinz F, Schlange T, Asadullah K. Believe it or not: how much can we rely on published data on potential drug targets? Nat Rev Drug Discov. 2011;10(9):712.

    Article  CAS  PubMed  Google Scholar 

  35. Koboziev I, Jones-Hall Y, Valentine JF, Reinoso WC, Furr KL, Grisham MB. Use of humanized mice to study the pathogenesis of autoimmune and inflammatory diseases. Inflamm Bowel Dis. 2015;21(7):1652–73.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bramhall M, Florez-Vargas O, Stevens R, Brass A, Cruickshank S. Quality of methods reporting in animal models of colitis. Inflamm Bowel Dis. 2015;21(6):1248–59.

    PubMed  PubMed Central  Google Scholar 

  37. Ey B, Eyking A, Klepak M, Salzman NH, Gothert JR, Runzi M, et al. Loss of TLR2 worsens spontaneous colitis in MDR1A deficiency through commensally induced pyroptosis. J Immunol. 2013;190(11):5676–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Feng T, Wang L, Schoeb TR, Elson CO, Cong Y. Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis. J Exp Med. 2010;207(6):1321–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Powrie F. T cells in inflammatory bowel disease: protective and pathogenic roles. Immunity. 1995;3(2):171–4.

    Article  CAS  PubMed  Google Scholar 

  40. Powrie F, Read S, Mottet C, Uhlig H, Maloy K. Control of immune pathology by regulatory T cells. Novartis Found Symp. 2003;252:92–8.

    Article  CAS  PubMed  Google Scholar 

  41. Powrie F, Leach MW, Mauze S, Caddle LB, Coffman RL. Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. Int Immunol. 1993;5(11):1461–71.

    Article  CAS  PubMed  Google Scholar 

  42. Ostanin DV, Bao J, Koboziev I, Gray L, Robinson-Jackson SA, Kosloski-Davidson M, et al. T cell transfer model of chronic colitis: concepts, considerations, and tricks of the trade. Am J Physiol Gastrointest Liver Physiol. 2009;296(2):G135–46.

    Article  CAS  PubMed  Google Scholar 

  43. Ostanin DV, Pavlick KP, Bharwani S, D'Souza D, Furr KL, Brown CM, et al. T cell-induced inflammation of the small and large intestine in immunodeficient mice. Am J Physiol Gastrointest Liver Physiol. 2006;290(1):G109–19.

    Article  CAS  PubMed  Google Scholar 

  44. Kanai T, Kawamura T, Dohi T, Makita S, Nemoto Y, Totsuka T, et al. TH1/TH2-mediated colitis induced by adoptive transfer of CD4 + CD45RBhigh T lymphocytes into nude mice. Inflamm Bowel Dis. 2006;12(2):89–99.

    Article  PubMed  Google Scholar 

  45. Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002;16(2):219–30.

    Article  CAS  PubMed  Google Scholar 

  46. Mizoguchi E, Mizoguchi A, Preffer FI, Bhan AK. Regulatory role of mature B cells in a murine model of inflammatory bowel disease. Int Immunol. 2000;12(5):597–605.

    Article  CAS  PubMed  Google Scholar 

  47. Dohi T, Fujihashi K, Koga T, Shirai Y, Kawamura YI, Ejima C, et al. T helper type-2 cells induce ileal villus atrophy, goblet cell metaplasia, and wasting disease in T cell-deficient mice. Gastroenterology. 2003;124(3):672–82.

    Article  CAS  PubMed  Google Scholar 

  48. Dohi T, Fujihashi K, Koga T, Etani Y, Yoshino N, Kawamura YI, et al. CD4 + CD45RBHi interleukin-4 defective T cells elicit antral gastritis and duodenitis. Am J Pathol. 2004;165(4):1257–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Nemoto Y, Kanai T, Takahara M, Oshima S, Okamoto R, Tsuchiya K, et al. Th1/Th17-mediated interstitial pneumonia in chronic colitis mice independent of intestinal microbiota. J Immunol. 2013;190(12):6616–25.

    Article  CAS  PubMed  Google Scholar 

  50. Hirano D, Kudo S. Usefulness of CD4 + CD45RBhigh. J Pharmacol Sci. 2009;110(2):169–81.

    Article  CAS  PubMed  Google Scholar 

  51. Dan N, Kanai T, Totsuka T, Iiyama R, Yamazaki M, Sawada T, et al. Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis. Am J Physiol Gastrointest Liver Physiol. 2003;285(4):G754–60.

    Article  CAS  PubMed  Google Scholar 

  52. Fujii R, Kanai T, Nemoto Y, Makita S, Oshima S, Okamoto R, et al. FTY720 suppresses CD4 + CD44highC. Am J Physiol Gastrointest Liver Physiol. 2006;291(2):G267–74.

    Article  CAS  PubMed  Google Scholar 

  53. Kanai T, Totsuka T, Uraushihara K, Makita S, Nakamura T, Koganei K, et al. Blockade of B7-H1 suppresses the development of chronic intestinal inflammation. J Immunol. 2003;171(8):4156–63.

    Article  CAS  PubMed  Google Scholar 

  54. Leon F, Contractor N, Fuss I, Marth T, Lahey E, Iwaki S, et al. Antibodies to complement receptor 3 treat established inflammation in murine models of colitis and a novel model of psoriasiform dermatitis. J Immunol. 2006;177(10):6974–82.

    Article  CAS  PubMed  Google Scholar 

  55. Liu Z, Geboes K, Colpaert S, Overbergh L, Mathieu C, Heremans H, et al. Prevention of experimental colitis in SCID mice reconstituted with CD45RBhigh CD4+ T cells by blocking the CD40 − CD154 interactions. J Immunol. 2000;164(11):6005–14.

    Article  CAS  PubMed  Google Scholar 

  56. Manocha M, Rietdijk S, Laouar A, Liao G, Bhan A, Borst J, et al. Blocking CD27 − CD70 costimulatory pathway suppresses experimental colitis. J Immunol. 2009;183(1):270–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Totsuka T, Kanai T, Uraushihara K, Iiyama R, Yamazaki M, Akiba H, et al. Therapeutic effect of anti-OX40L and anti-TNF-alpha MAbs in a murine model of chronic colitis. Am J Physiol Gastrointest Liver Physiol. 2003;284(4):G595–603.

    Article  CAS  PubMed  Google Scholar 

  58. Barnes MJ, Powrie F. Regulatory T cells reinforce intestinal homeostasis. Immunity. 2009;31(3):401–11.

    Article  CAS  PubMed  Google Scholar 

  59. Izcue A, Coombes JL, Powrie F. Regulatory lymphocytes and intestinal inflammation. Annu Rev Immunol. 2009;27:313–38.

    Article  CAS  PubMed  Google Scholar 

  60. Karlsson F, Robinson-Jackson SA, Gray L, Zhang S, Grisham MB. Ex vivo generation of regulatory T cells: characterization and therapeutic evaluation in a model of chronic colitis. Methods Mol Biol. 2011;677:47–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Karlsson F, Martinez NE, Gray L, Zhang S, Tsunoda I, Grisham MB. Therapeutic evaluation of ex vivo-generated versus natural regulatory T-cells in a mouse model of chronic gut inflammation. Inflamm Bowel Dis. 2013;19(11):2282–94.

    Article  PubMed  Google Scholar 

  62. Fang K, Zhang S, Glawe J, Grisham MB, Kevil CG. Temporal genome expression profile analysis during t-cell-mediated colitis: identification of novel targets and pathways. Inflamm Bowel Dis. 2012;18(8):1411–23.

    Article  PubMed  Google Scholar 

  63. Fang K, Grisham MB, Kevil CG. Application of comparative transcriptional genomics to identify molecular targets for pediatric IBD. Front Immunol. 2015;6:165.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Berg DJ, Davidson N, Kuhn R, Muller W, Menon S, Holland G, et al. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest. 1996;98(4):1010–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75(2):263–74.

    Article  CAS  PubMed  Google Scholar 

  66. Hickey CA, Kuhn KA, Donermeyer DL, Porter NT, Jin C, Cameron EA, et al. Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles. Cell Host Microbe. 2015;17(5):672–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kang SS, Bloom SM, Norian LA, Geske MJ, Flavell RA, Stappenbeck TS, et al. An antibiotic-responsive mouse model of fulminant ulcerative colitis. PLoS Med. 2008;5(3), e41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bloom SM, Bijanki VN, Nava GM, Sun L, Malvin NP, Donermeyer DL, et al. Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe. 2011;9(5):390–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Glocker EO, Kotlarz D, Boztug K, Gertz EM, Schaffer AA, Noyan F, et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 2009;361(21):2033–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wilk JN, Bilsborough J, Viney JL. The mdr1a−/− mouse model of spontaneous colitis: a relevant and appropriate animal model to study inflammatory bowel disease. Immunol Res. 2005;31(2):151–9.

    Article  CAS  PubMed  Google Scholar 

  72. Panwala CM, Jones JC, Viney JL. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J Immunol. 1998;161(10):5733–44.

    CAS  PubMed  Google Scholar 

  73. Collett A, Higgs NB, Gironella M, Zeef LA, Hayes A, Salmo E, et al. Early molecular and functional changes in colonic epithelium that precede increased gut permeability during colitis development in mdr1a(−/−) mice. Inflamm Bowel Dis. 2008;14(5):620–31.

    Article  PubMed  Google Scholar 

  74. Tanner SM, Staley EM, Lorenz RG. Altered generation of induced regulatory T cells in the FVB.mdr1a−/− mouse model of colitis. Mucosal Immunol. 2013;6(2):309–23.

    Article  CAS  PubMed  Google Scholar 

  75. Staley EM, Schoeb TR, Lorenz RG. Differential susceptibility of P-glycoprotein deficient mice to colitis induction by environmental insults. Inflamm Bowel Dis. 2009;15(5):684–96.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Pallis M, Turzanski J, Higashi Y, Russell N. P-glycoprotein in acute myeloid leukaemia: therapeutic implications of its association with both a multidrug-resistant and an apoptosis-resistant phenotype. Leuk Lymphoma. 2002;43(6):1221–8.

    Article  CAS  PubMed  Google Scholar 

  77. Pierik M, Joossens S, Van SK, Van SN, Vlietinck R, Rutgeerts P, et al. Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis. 2006;12(1):1–8.

    Article  PubMed  Google Scholar 

  78. Maloy KJ, Salaun L, Cahill R, Dougan G, Saunders NJ, Powrie F. CD4 + CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med. 2003;197(1):111–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Uhlig HH, McKenzie BS, Hue S, Thompson C, Joyce-Shaikh B, Stepankova R, et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity. 2006;25(2):309–18.

    Article  CAS  PubMed  Google Scholar 

  80. Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med. 2006;203(11):2473–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Asquith DL, Miller AM, McInnes IB, Liew FY. Animal models of rheumatoid arthritis. 2009;2009/08/13(8):2040–4.

    Google Scholar 

  82. Boulard O, Asquith MJ, Powrie F, Maloy KJ. TLR2-independent induction and regulation of chronic intestinal inflammation. Eur J Immunol. 2010;40(2):516–24.

    Article  CAS  PubMed  Google Scholar 

  83. Kullberg MC, Jankovic D, Feng CG, Hue S, Gorelick PL, McKenzie BS, et al. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J Exp Med. 2006;203(11):2485–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, et al. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. 2007;131(1):33–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, Delaney ML, et al. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe. 2010;8(3):292–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Cooper R, Fraser SM, Sturrock RD, Gemmell CG. Raised titres of anti-klebsiella IgA in ankylosing spondylitis, rheumatoid arthritis, and inflammatory bowel disease. Br Med J (Clin Res Ed). 1988;296(6634):1432–4.

    Article  CAS  Google Scholar 

  87. Kanareykina SK, Misautova AA, Zlatkina AR, Levina EN. Proteus dysbioses in patients with ulcerative colitis. Nahrung. 1987;31(5–6):557–61.

    Article  CAS  PubMed  Google Scholar 

  88. Rooks MG, Veiga P, Wardwell-Scott LH, Tickle T, Segata N, Michaud M, et al. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission. ISME J. 2014;8(7):1403–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Winter SE, Thiennimitr P, Winter MG, Butler BP, Huseby DL, Crawford RW, et al. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature. 2010;467(7314):426–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Winter SE, Winter MG, Xavier MN, Thiennimitr P, Poon V, Keestra AM, et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science. 2013;339(6120):708–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Garrett WS, Punit S, Gallini CA, Michaud M, Zhang D, Sigrist KS, et al. Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell. 2009;16(3):208–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ermann J, Garrett WS, Kuchroo J, Rourida K, Glickman JN, Bleich A, et al. Severity of innate immune-mediated colitis is controlled by the cytokine deficiency-induced colitis susceptibility-1 (Cdcs1) locus. Proc Natl Acad Sci U S A. 2011;108(17):7137–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Borm ME, He J, Kelsall B, Pena AS, Strober W, Bouma G. A major quantitative trait locus on mouse chromosome 3 is involved in disease susceptibility in different colitis models. Gastroenterology. 2005;128(1):74–85.

    Article  CAS  PubMed  Google Scholar 

  94. Kontoyiannis D, Pasparakis M, Pizarro TT, Cominelli F, Kollias G. Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity. 1999;10(3):387–98.

    Article  CAS  PubMed  Google Scholar 

  95. Baur P, Martin FP, Gruber L, Bosco N, Brahmbhatt V, Collino S, et al. Metabolic phenotyping of the Crohn’s disease-like IBD etiopathology in the TNF(DeltaARE/WT) mouse model. J Proteome Res. 2011;10(12):5523–35.

    Article  CAS  PubMed  Google Scholar 

  96. Huybers S, Apostolaki M, van der Eerden BC, Kollias G, Naber TH, Bindels RJ, et al. Murine TNF(DeltaARE) Crohn’s disease model displays diminished expression of intestinal Ca2+ transporters. Inflamm Bowel Dis. 2008;14(6):803–11.

    Article  PubMed  Google Scholar 

  97. Schaubeck M, Clavel T, Calasan J, Lagkouvardos I, Haange SB, Jehmlich N, et al. Dysbiotic gut microbiota causes transmissible Crohn’s disease-like ileitis independent of failure in antimicrobial defence. Gut. 2015 Apr 17.

    Google Scholar 

  98. Werner T, Wagner SJ, Martinez I, Walter J, Chang JS, Clavel T, et al. Depletion of luminal iron alters the gut microbiota and prevents Crohn’s disease-like ileitis. Gut. 2011;60(3):325–33.

    Article  CAS  PubMed  Google Scholar 

  99. Matsumoto S, Okabe Y, Setoyama H, Takayama K, Ohtsuka J, Funahashi H, et al. Inflammatory bowel disease-like enteritis and caecitis in a senescence accelerated mouse P1/Yit strain. Gut. 1998;43(1):71–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kosiewicz MM, Nast CC, Krishnan A, Rivera-Nieves J, Moskaluk CA, Matsumoto S, et al. Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn’s disease. J Clin Invest. 2001;107(6):695–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Pietropaoli D, Del PR, Corridoni D, Rodriguez-Palacios A, Di SG, Monaco A, et al. Occurrence of spontaneous periodontal disease in the SAMP1/YitFc murine model of Crohn disease. J Periodontol. 2014;85(12):1799–805.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Rivera-Nieves J, Bamias G, Vidrich A, Marini M, Pizarro TT, McDuffie MJ, et al. Emergence of perianal fistulizing disease in the SAMP1/YitFc mouse, a spontaneous model of chronic ileitis. Gastroenterology. 2003;124(4):972–82.

    Article  PubMed  Google Scholar 

  103. Pizarro TT, Pastorelli L, Bamias G, Garg RR, Reuter BK, Mercado JR, et al. SAMP1/YitFc mouse strain: a spontaneous model of Crohn’s disease-like ileitis. Inflamm Bowel Dis. 2011;17(12):2566–84.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Ishikawa D, Okazawa A, Corridoni D, Jia LG, Wang XM, Guanzon M, et al. Tregs are dysfunctional in vivo in a spontaneous murine model of Crohn’s disease. Mucosal Immunol. 2013;6(2):267–75.

    Article  CAS  PubMed  Google Scholar 

  105. Saruta M, Yu QT, Fleshner PR, Mantel PY, Schmidt-Weber CB, Banham AH, et al. Characterization of FOXP3 + CD4+ regulatory T cells in Crohn’s disease. Clin Immunol. 2007;125(3):281–90.

    Article  CAS  PubMed  Google Scholar 

  106. Fantini MC, Rizzo A, Fina D, Caruso R, Sarra M, Stolfi C, et al. Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression. Gastroenterology. 2009;136(4):1308–16.

    Article  CAS  PubMed  Google Scholar 

  107. Corridoni D, Kodani T, Rodriguez-Palacios A, Pizarro TT, Xin W, Nickerson KP, et al. Dysregulated NOD2 predisposes SAMP1/YitFc mice to chronic intestinal inflammation. Proc Natl Acad Sci U S A. 2013;110(42):16999–7004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Corridoni D, Arseneau KO, Cominelli F. Functional defects in NOD2 signaling in experimental and human Crohn disease. Gut Microbes. 2014;5(3):340–4.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Brehm MA, Shultz LD, Greiner DL. Humanized mouse models to study human diseases. Curr Opin Endocrinol Diabetes Obes. 2010;17(2):120–5.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Shultz LD, Ishikawa F, Greiner DL. Humanized mice in translational biomedical research. Nat Rev Immunol. 2007;7(2):118–30.

    Article  CAS  PubMed  Google Scholar 

  111. Shultz LD, Brehm MA, Bavari S, Greiner DL. Humanized mice as a preclinical tool for infectious disease and biomedical research. Ann N Y Acad Sci. 2011;1245:50–4.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Shultz LD, Brehm MA, Garcia-Martinez JV, Greiner DL. Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol. 2012;12(11):786–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Haley PJ. Species differences in the structure and function of the immune system. Toxicology. 2003;188(1):49–71.

    Article  CAS  PubMed  Google Scholar 

  114. Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol. 2004;172(5):2731–8.

    Article  CAS  PubMed  Google Scholar 

  115. Brehm MA, Jouvet N, Greiner DL, Shultz LD. Humanized mice for the study of infectious diseases. Curr Opin Immunol. 2013 Jun 7.

    Google Scholar 

  116. Brehm MA, Wiles MV, Greiner DL, Shultz LD. Generation of improved humanized mouse models for human infectious diseases. J Immunol Methods. 2014 Mar 4.

    Google Scholar 

  117. Pearson T, Greiner DL, Shultz LD. Creation of “humanized” mice to study human immunity. Curr Protoc Immunol. 2008;Chapter 15:Unit.

    Google Scholar 

  118. Zhou Q, Facciponte J, Jin M, Shen Q, Lin Q. Humanized NOD-SCID IL2rg−/− mice as a preclinical model for cancer research and its potential use for individualized cancer therapies. Cancer Lett. 2014;344(1):13–9.

    Article  CAS  PubMed  Google Scholar 

  119. Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G, et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood. 2005;106(5):1565–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, et al. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002;100(9):3175–82.

    Article  CAS  PubMed  Google Scholar 

  121. Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174(10):6477–89.

    Article  CAS  PubMed  Google Scholar 

  122. Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti JC, Lanzavecchia A, et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science. 2004;304(5667):104–7.

    Article  CAS  PubMed  Google Scholar 

  123. DiSanto JP, Muller W, Guy-Grand D, Fischer A, Rajewsky K. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc Natl Acad Sci U S A. 1995;92(2):377–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Sugamura K, Asao H, Kondo M, Tanaka N, Ishii N, Ohbo K, et al. The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu Rev Immunol. 1996;14:179–205.

    Article  CAS  PubMed  Google Scholar 

  125. Kovanen PE, Leonard WJ. Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways. Immunol Rev. 2004;202:67–83.

    Article  CAS  PubMed  Google Scholar 

  126. Leonard WJ. Cytokines and immunodeficiency diseases. Nat Rev Immunol. 2001;1(3):200–8.

    Article  CAS  PubMed  Google Scholar 

  127. Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol. 2009;9(7):480–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Brehm MA, Cuthbert A, Yang C, Miller DM, Diiorio P, Laning J, et al. Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation. Clin Immunol. 2010;135(1):84–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. McDermott SP, Eppert K, Lechman ER, Doedens M, Dick JE. Comparison of human cord blood engraftment between immunocompromised mouse strains. Blood. 2010;116(2):193–200.

    Article  CAS  PubMed  Google Scholar 

  130. Mosier DE, Gulizia RJ, Baird SM, Wilson DB. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 1988;335(6187):256–9.

    Article  CAS  PubMed  Google Scholar 

  131. Bock TA, Orlic D, Dunbar CE, Broxmeyer HE, Bodine DM. Improved engraftment of human hematopoietic cells in severe combined immunodeficient (SCID) mice carrying human cytokine transgenes. J Exp Med. 1995;182(6):2037–43.

    Article  CAS  PubMed  Google Scholar 

  132. Greiner DL, Hesselton RA, Shultz LD. SCID mouse models of human stem cell engraftment. Stem Cells. 1998;16(3):166–77.

    Article  CAS  PubMed  Google Scholar 

  133. Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB, Tennent B, et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol. 1995;154(1):180–91.

    CAS  PubMed  Google Scholar 

  134. Hogenes M, Huibers M, Kroone C, de WR. Humanized mouse models in transplantation research. Transplant Rev (Orlando). 2014;28(3):103–10.

    Google Scholar 

  135. Shultz LD, Pearson T, King M, Giassi L, Carney L, Gott B, et al. Humanized NOD/LtSz-scid IL2 receptor common gamma chain knockout mice in diabetes research. Ann N Y Acad Sci. 2007;1103:77–89.

    Article  CAS  PubMed  Google Scholar 

  136. King M, Pearson T, Shultz LD, Leif J, Bottino R, Trucco M, et al. A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene. Clin Immunol. 2008;126(3):303–14.

    Article  CAS  PubMed  Google Scholar 

  137. Brehm MA, Shultz LD, Luban J, Greiner DL. Overcoming current limitations in humanized mouse research. J Infect Dis. 2013;208 Suppl 2:S125–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Spranger S, Frankenberger B, Schendel DJ. NOD/scid IL-2Rg(null) mice: a preclinical model system to evaluate human dendritic cell-based vaccine strategies in vivo. J Transl Med. 2012;10:30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. King MA, Covassin L, Brehm MA, Racki W, Pearson T, Leif J, et al. Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex. Clin Exp Immunol. 2009;157(1):104–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Lepus CM, Gibson TF, Gerber SA, Kawikova I, Szczepanik M, Hossain J, et al. Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac-/-, Balb/c-Rag1-/-gammac-/-, and C.B-17-scid/bg immunodeficient mice. 2009;2009/06/16(10):790–802.

    Google Scholar 

  141. Matsumura T, Kametani Y, Ando K, Hirano Y, Katano I, Ito R, et al. Functional CD5+ B cells develop predominantly in the spleen of NOD/SCID/gammac(null) (NOG) mice transplanted either with human umbilical cord blood, bone marrow, or mobilized peripheral blood CD34+ cells. Exp Hematol. 2003;31(9):789–97.

    Article  PubMed  Google Scholar 

  142. Choi B, Chun E, Kim M, Kim SY, Kim ST, Yoon K, et al. Human T cell development in the liver of humanized NOD/SCID/IL-2Rgamma(null)(NSG) mice generated by intrahepatic injection of CD34(+) human (h) cord blood (CB) cells. Clin Immunol. 2011;139(3):321–35.

    Article  CAS  PubMed  Google Scholar 

  143. Misharin AV, Haines III GK, Rose S, Gierut AK, Hotchkiss RS, Perlman H. Development of a new humanized mouse model to study acute inflammatory arthritis. J Transl Med. 2012;10:190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Yahata T, Ando K, Nakamura Y, Ueyama Y, Shimamura K, Tamaoki N, et al. Functional human T lymphocyte development from cord blood CD34+ cells in nonobese diabetic/Shi-scid, IL-2 receptor gamma null mice. J Immunol. 2002;169(1):204–9.

    Article  CAS  PubMed  Google Scholar 

  145. Tanaka S, Saito Y, Kunisawa J, Kurashima Y, Wake T, Suzuki N, et al. Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rgammaKO mice. J Immunol (Baltimore, MD: 1950). 2012;2012/05/23:6145–55.

    Google Scholar 

  146. Lapidot T, Pflumio F, Doedens M, Murdoch B, Williams DE, Dick JE. Cytokine stimulation of multilineage hematopoiesis from immature human cells engrafted in SCID mice. Science. 1992;255(5048):1137–41.

    Article  CAS  PubMed  Google Scholar 

  147. Watanabe Y, Takahashi T, Okajima A, Shiokawa M, Ishii N, Katano I, et al. The analysis of the functions of human B and T cells in humanized NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice). Int Immunol. 2009;21(7):843–58.

    Article  CAS  PubMed  Google Scholar 

  148. Lan P, Tonomura N, Shimizu A, Wang S, Yang YG. Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation. Blood. 2006;108(2):487–92.

    Article  CAS  PubMed  Google Scholar 

  149. Melkus MW, Estes JD, Padgett-Thomas A, Gatlin J, Denton PW, Othieno FA, et al. Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat Med. 2006;12(11):1316–22.

    Article  CAS  PubMed  Google Scholar 

  150. Covassin L, Jangalwe S, Jouvet N, Laning J, Burzenski L, Shultz LD, et al. Human immune system development and survival of NOD-scid IL2rgamma (NSG) mice engrafted with human thymus and autologous hematopoietic stem cells. Clin Exp Immunol. 2013 Jul 19.

    Google Scholar 

  151. Tonomura N, Habiro K, Shimizu A, Sykes M, Yang YG. Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model. Blood. 2008;111(8):4293–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Brainard DM, Seung E, Frahm N, Cariappa A, Bailey CC, Hart WK, et al. Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice. J Virol. 2009;83(14):7305–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Denton PW, Nochi T, Lim A, Krisko JF, Martinez-Torres F, Choudhary SK, et al. IL-2 receptor gamma-chain molecule is critical for intestinal T-cell reconstitution in humanized mice. Mucosal Immunol. 2012;5(5):555–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Strowig T, Rongvaux A, Rathinam C, Takizawa H, Borsotti C, Philbrick W, et al. Transgenic expression of human signal regulatory protein alpha in Rag2-/-gamma(c)-/- mice improves engraftment of human hematopoietic cells in humanized mice. Proceedings National Academy of Sciences. 2011;108:13218–23.

    Google Scholar 

  155. Stoddart CA, Maidji E, Galkina SA, Kosikova G, Rivera JM, Moreno ME, et al. Superior human leukocyte reconstitution and susceptibility to vaginal HIV transmission in humanized NOD-scid IL-2Rgamma(-/-) (NSG) BLT mice. Virology. 2011;417(1):154–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Nochi T, Denton PW, Wahl A, Garcia JV. Cryptopatches are essential for the development of human GALT. Cell Rep. 2013;3:1874–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Rajesh D, Zhou Y, Jankowska-Gan E, Roenneburg DA, Dart ML, Torrealba J, et al. Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rgammanull mice. Hum Immunol. 2010;71(6):551–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Villaudy J, Schotte R, Legrand N, Spits H. Critical assessment of human antibody generation in humanized mouse models. J Immunol Methods. 2014;410:18–27.

    Article  CAS  PubMed  Google Scholar 

  159. Ali N, Flutter B, Sanchez RR, Sharif-Paghaleh E, Barber LD, Lombardi G, et al. Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rgammanull mice display a T-effector memory phenotype. PLoS One. 2012;7(8), e44219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Greenblatt MB, Vrbanac V, Tivey T, Tsang K, Tager AM, Aliprantis AO. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model. 2012;2012/09/08(9):e44664.

    Google Scholar 

  161. Lockridge JL, Zhou Y, Becker YA, Ma S, Kenney SC, Hematti P, et al. Mice engrafted with human fetal thymic tissue and hematopoietic stem cells develop pathology resembling chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2013;19(9):1310–22.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Lavender KJ, Pang WW, Messer RJ, Duley AK, Race B, Phillips K, et al. BLT-humanized C57BL/6 Rag2-/-gammac-/-CD47-/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection. Blood. 2013;122(25):4013–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Lavender KJ, Messer RJ, Race B, Hasenkrug KJ. Production of bone marrow, liver, thymus (BLT) humanized mice on the C57BL/6 Rag2(-/-)gammac(-/-)CD47(-/-) background. J Immunol Methods. 2014;407:127–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Nolte T, Zadeh-Khorasani M, Safarov O, Rueff F, Gülberg V, Herbach N, et al. Oxazolone and ethanol induce colitis in non-obese diabetic-severe combined immunodeficiency interleukin-2Rγ(null) mice engrafted with human peripheral blood mononuclear cells. 2013;172:349–62.

    Google Scholar 

  165. Nolte T, Zadeh-Khorasani M, Safarov O, Rueff F, Varga R, Herbach N, et al. Induction of oxazolone-mediated features of atopic dermatitis in NOD-scid IL2Rgamma(null) mice engrafted with human peripheral blood mononuclear cells. Dis Model Mech. 2013;6(1):125–34.

    Article  CAS  PubMed  Google Scholar 

  166. Goettel JA, Biswas S, Lexmond WS, YUeste A, Passerinin L, Patel B, Yang S, Sun J, Ouahed J, et. al. Fatal autoimmunity inmice reconsitituted with human hematopoietic stem cells encouding defective FOXP3. Blood. 2015;125(25):3886–95.

    Google Scholar 

  167. Goettel JA, Biswas S, Lexmond WS, Sun J, Ouahed J, McCann K, et al. Human hematopoietic stem cells with a defined immunodeficiency and enteropathy transfer clinical phenotype to a novel humanized mouse strain. Inflamm Bowel Dis. 2014;146:S-81.

    Google Scholar 

  168. Jess T, Riis L, Jespersgaard C, Hougs L, Andersen PS, Orholm MK, et al. Disease concordance, zygosity, and NOD2/CARD15 status: follow-up of a population-based cohort of Danish twins with inflammatory bowel disease. Am J Gastroenterol. 2005;100:2486–92.

    Article  CAS  PubMed  Google Scholar 

  169. Bernstein CN, Shanahan F. Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut. 2008;57(9):1185–91.

    Article  PubMed  Google Scholar 

  170. Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1785–94.

    Article  PubMed  Google Scholar 

  171. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46–54.

    Article  PubMed  Google Scholar 

  173. Ventham NT, Kennedy NA, Nimmo ER, Satsangi J. Beyond gene discovery in inflammatory bowel disease: the emerging role of epigenetics. Gastroenterology. 2013 Jun 8.

    Google Scholar 

  174. Chung H, Pamp SJ, Hill JA, Surana NK, Edelman SM, Troy EB, et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012;149(7):1578–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Hintze KJ, Cox JE, Rompato G, Benninghoff AD, Ward RE, Broadbent J, et al. Broad scope method for creating humanized animal models for animal health and disease research through antibiotic treatment and human fecal transfer. 2014;5:183–91.

    Google Scholar 

  176. Zheng J, Liu Y, Liu Y, Liu M, Xiang Z, Lam KT, et al. Human CD8+ regulatory T cells inhibit GVHD and preserve general immunity in humanized mice. Sci Transl Med. 2013;5:168ra9.

    PubMed  Google Scholar 

Download references

Acknowledgements

Some of the work reported in this manuscript was supported by a grant from DOD (W81XWH-11-1-0666; MBG) and the NIH (R01-DK091269; MBG).

Some of this chapter was reproduced from a review entitled “Pharmacological Intervention Studies Using Mouse Models of the Inflammatory Bowel Diseases:

Translating Preclinical Data into New Drug Therapies” published in Inflammatory Bowel Diseases, 2011. This material is reproduced with permission of John Wiley and Sons, Inc.

Author information

Authors and Affiliations

  1. Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, 3601 4th Street STOP 6591, Lubbock, TX, 79430-6591, USA

    Cynthia Reinoso Webb B.S., M(ASCP) & Matthew B. Grisham Ph.D.

Authors
  1. Cynthia Reinoso Webb B.S., M(ASCP)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew B. Grisham Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew B. Grisham Ph.D. .

Editor information

Editors and Affiliations

  1. Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Charité Medical School—Humboldt-University of Berlin, Berlin, Germany

    Daniel C. Baumgart

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Webb, C.R., Grisham, M.B. (2017). Mouse Models of Chronic Intestinal Inflammation: Characterization and Use in Pharmacological Intervention Studies. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Cham. https://doi.org/10.1007/978-3-319-33703-6_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-33703-6_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-33701-2

  • Online ISBN: 978-3-319-33703-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation