Skip to main content

Advertisement

SpringerLink
Log in

Animal models of inflammatory bowel disease: a review

  • Review
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

Abstract

Inflammatory bowel disease (IBD) represents a group of idiopathic chronic inflammatory intestinal conditions associated with various areas of the GI tract, including two types of inflammatory conditions, i.e., ulcerative colitis (UC) and Crohn’s disease (CD). Both UC and CD are chronic inflammatory disorders of the intestine; in UC, inflammation starts in the rectum and generally extends proximally in a continuous manner through the entire colon. Bloody diarrhea, presence of blood and mucus mixed with stool, accompanied by lower abdominal cramping, are the characteristic symptoms of the disease. While in CD, inflammatory condition may affect any part of the GI tract from mouth to anus. It mainly causes abdominal pain, diarrhea, vomiting and weight loss. Although the basic etiology of IBD is unknown, there are several factors that may contribute to the pathogenesis of this disease, such as dysregulation of immune system or commensal bacteria, oxidative stress and inflammatory mediators. In order to understand these different etiological factors, a number of experimental models are available in the scientific research, including chemical-induced, spontaneous, genetically engineered and transgenic models. These models represent a major source of information about biological systems and are clinically relevant to the human IBD. Since there is less collective data available in one single article discussing about all these models, in this review an effort is made to study the outline of pathophysiology and various types of animal models used in the research study of IBD and other disease-related complications.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Aleisa AM, Al-Rejaie SS, Abuohashish HM, Ola MS, Parmar MY, Ahmed MM (2014) Pretreatment of Gymnema sylvestre revealed the protection against acetic acid-induced ulcerative colitis in rats. BMC Complement Altern Med 14(1):49

    PubMed Central  PubMed  Google Scholar 

  • Algieri F, Rodriguez-Nogales A, Garrido-Mesa N, Zorrilla P, Burkard N, Pischel I, Sievers H et al (2014) Intestinal anti-inflammatory activity of the Serpylli herba extract in experimental models of rodent colitis. J Crohns Colitis. doi:10.1016/j.crohns.2013.12.012

    PubMed  Google Scholar 

  • Al-Rejaie SS, Abuohashish HM, Al-Enazi MM, Al-Assaf AH, Parmar MY, Ahmed MM (2013) Protective effect of naringenin on acetic acid-induced ulcerative colitis in rats. World J Gastroentero 19(34):5633

    CAS  Google Scholar 

  • Araki Y, Mukaisyo K, Sugihara H, Fujiyama Y, Hattori T (2010) Increased apoptosis and decreased proliferation of colonic epithelium in dextran sulfate sodium-induced colitis in mice. Oncol Rep 24(4):869–874

    CAS  PubMed  Google Scholar 

  • Arthur K, Zeissig S, Blumberg RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28:573–621

    Google Scholar 

  • Baribault H, Penner J, Iozzo RV, Wilson-Heiner M (1994) Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice. Genes Dev 8:2964–2973

    CAS  PubMed  Google Scholar 

  • Barnett M, Fraser A (2011) Animal models of colitis: lessons learned, and their relevance to the clinic. In: Connor M (ed) Ulcerative colitis—treatments, special populations and the future. InTech, ISBN: 978-953-307-739-0

  • Baumgart DC, Sandborn WJ (2012) Crohn’s disease. Lancet 380(9853):1590–1605

    PubMed  Google Scholar 

  • Baumgart DC, Olivier WA, Reya T, Peritt D, Rombeau JL, Carding SR (1998) Mechanisms of intestinal epithelial cell injury and colitis in interleukin 2 (IL2)-deficient mice. Cell Immunol 187:52–66

    CAS  PubMed  Google Scholar 

  • Behera JP, Mohanty B, Ramani YR, Rath B, Pradhan S (2012) Effect of aqueous extract of Aegle marmelos unripe fruit on inflammatory bowel disease. Indian J Pharmacol 44(5):614

    PubMed Central  PubMed  Google Scholar 

  • Beisner J, Stange ED, Wehkamp J (2010) Innate antimicrobial immunity in inflammatory bowel diseases. Expert Rev Clin Immunol 6(5):809–818

    CAS  PubMed  Google Scholar 

  • Benard C, Cultrone A, Michel C, Rosales C, Segain JP, Lahaye M, Galmiche JP, Cherbut C, Blottière HM (2010) Degraded carrageenan causing colitis in rats induces TNF secretion and ICAM-1 upregulation in monocytes through NF-κB activation. PLoS ONE 5(1):e8666

    PubMed Central  PubMed  Google Scholar 

  • Berg DJ, Davidson N, Kuhn R, Muller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D (1996) Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest 98:1010–1020

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bhattacharyya S, Borthakur A, Anbazhagan AN, Katyal S, Dudeja PK, Tobacman JK (2011) Specific effects of BCL10 Serine mutations on phosphorylations in canonical and noncanonical pathways of NF-κB activation following carrageenan. Am J Physiol Gastrointest Liver Physiol 301(3):G475–G486

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boirivant M, Fuss IJ, Chu A, Strober W (1998) Oxazolone colitis: a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. J Exp Med 188(10):1929–1939

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boismenu R, Chen Y (2000) Insights from mouse models of colitis. J Leukocyte Biol 67:267–278

    CAS  PubMed  Google Scholar 

  • Borthakur A, Bhattacharyya S, Dudeja PK, Tobacman JK (2007) Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 292(3):G829–G838

    CAS  PubMed  Google Scholar 

  • Borthakur A, Bhattacharyya S, Anbazhagan AN, Kumar A, Dudeja PK, Tobacman JK (2012) Prolongation of carrageenan-induced inflammation in human colonic epithelial cells by activation of an NFκB-BCL10 loop. Biochim Biophys Acta-Mol Basis Dis 1822(8):1300–1307

    CAS  Google Scholar 

  • Brenna O, Furnes MW, Drozdov I, Granlund AB, Flatberg A, Sandvik AK, Zwiggelaar RM et al (2013) Relevance of TNBS-colitis in rats: a methodological study with endoscopic, historical and transcripttomic characterization and correlation to IBD. PLoS ONE 8(1):e54543

    CAS  PubMed Central  PubMed  Google Scholar 

  • Burisch J (2014) Crohn’s disease and ulcerative colitis. Occurrence, course and prognosis during the first year of disease in a European population-based inception cohort. Dan Med J 61(1):B4778–B4778

    PubMed  Google Scholar 

  • Camuesco D, Rodríguez-Cabezas ME, Garrido-Mesa N, Cueto-Sola M, Bailón E, Comalada M, Arribas B et al (2012) The intestinal anti-inflammatory effect of dersalazine sodium is related to a down-regulation in IL-17 production in experimental models of rodent colitis. Br J Pharmacol 165(3):729–740

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cong Y, Brandwein S, McCabe R, Lazenby A, Birkenmeier E, Sundberg J, Elson C (1998) CD4+ T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: increased T helper cell type 1 response and ability to transfer disease. J Exp Med 187:855–864

    CAS  PubMed Central  PubMed  Google Scholar 

  • Coskun M, Olsen J, Seidelin JB, Nielsen OH (2011) MAP kinases in inflammatory bowel disease. Clin Chim Acta 412(7):513–520

    CAS  PubMed  Google Scholar 

  • Coskun M, Salem M, Pedersen J, Nielsen OH (2013) Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease. Pharmacol Res 76:1–8

    CAS  PubMed  Google Scholar 

  • Cuzzocrea S, McDonald MC, Mazzon E, Mota-Filipe H, Centorrino T, Terranova ML et al (2001) Calpain inhibitor I reduces colon injury caused by dinitrobenzene sulphonic acid in the rat. Gut 48:8–478

    Google Scholar 

  • Dalwadi H, Wei B, Schrage M, Spicher K, Su TT, Birnbaumer L, Rawlings DJ, Braun J (2003) B cell developmental requirement for the G alpha i2 gene. J Immunol 170:1707–1715

    CAS  PubMed  Google Scholar 

  • Danese S, Sans M, Fiocchi C (2004) Inflammatory bowel disease: the role of environmental factors. Autoimmun Rev 3:394–400

    CAS  PubMed  Google Scholar 

  • Darji VC, Deshpande SS, Bariya AH (2013) Comparison between the effect of aqueous and methanolic extracts of holarrhena antidysenterica bark against experimentally induced inflammatory bowel disease. Int J Pharm 4(1):131–134

    Google Scholar 

  • Darwish IE, Hala MM, Amany SO (2012) Study of possible colonic mucosal and motility changes in experimental acetic acid induced colitis in male albino rats under the effect of oral barley Administration in comparison with venlafaxine. J Physiol Pharmacol Adv 2(9):319–329

    Google Scholar 

  • Das S, Kanodia L, Mukherjee A, Hakim A (2013) Effect of ethanolic extract of leaves of Paederia foetida Linn on acetic acid induced colitis in albino rats. Indian J Pharmacol 45(5):453

    PubMed Central  PubMed  Google Scholar 

  • Dothel G, Vasina V, Barbara G, Ponti FD (2013) Animal models of chemically induced intestinal inflammation: predictivity and ethical issues. Pharmacol Ther 139(1):71–86

    CAS  PubMed  Google Scholar 

  • Dou W, Zhang J, Sun A, Zhang E, Ding L, Mukherjee S, Wei X, Chou G, Wang ZT, Mani S (2013) Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling. Brit J Nutr 110(4):599–608

    CAS  PubMed Central  PubMed  Google Scholar 

  • Edwards RA, Smock AZ (2006) Defective arachidonate release and PGE2 production in Gi alpha2-deficient intestinal and colonic subepithelial myofibroblasts. Inflamm Bowel Dis 12:153–165

    PubMed  Google Scholar 

  • Gutierrez O, Pipaon C, Inohara N, Fontalba A, Ogura Y, Prosper F, Nunez G, Fernandez-Luna JL (2002) Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation. J Biol Chem 277:41701–41705

    CAS  PubMed  Google Scholar 

  • Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, Oshima S, Barrera J, Huang EJ, Hou B, Malynn BA et al (2011) Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol 12:1184–1193

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hassan A, Ibrahim A, Mbodji K, Coëffier M, Ziegler F, Bounoure F, Chardigny JM et al (2010) An α-linolenic acid-rich formula reduces oxidative stress and inflammation by regulating NF-κB in rats with TNBS-induced colitis. J Nutr 140(10):1714–1721

    CAS  PubMed  Google Scholar 

  • Hemstreet BA (2010) Inflammatory bowel disease. Pharmacotherapy principles and practice, 3rd edn. McGraw Hill Professional, pp 359–374

  • Hermiston ML, Gordon JI (1995) Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science 270:1203–1207

    CAS  PubMed  Google Scholar 

  • Inagaki-Ohara K, Sasaki A, Matsuzaki G, Ikeda T, Hotokezaka M, Chijiiwa K, Kubo M, Yoshida H, Nawa Y, Yoshimura A (2006) Suppressor of cytokine signalling 1 in lymphocytes regulates the development of intestinal inflammation in mice. Gut 55:212–219

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jensen SR, Fink LN, Nielsen OH, Brynskov J, Brix S (2011) Ex vivo intestinal adhesion of Escherichia coli LF82 in Crohn’s disease. Microb Pathog 51(6):426–431

    CAS  PubMed  Google Scholar 

  • Jiang HL, Cui HF (2000) A new chronic ulcerative colitis model produced by combined methods in rats. World J Gastroentero 6(5):742–746

    Google Scholar 

  • Jiang XL, Quan QZ, Liu T, Dong XC (2000) Recent advances in research of ulcerative colitis. Shijie Huaren Xiaohua Zazhi 8:216–218

    Google Scholar 

  • Johnson C, Wannemuehler M, Hostetter J (2014) Mycobacterium avium paratuberculosis infection augments innate immune responses following intestinal epithelial injury. Exp Biol Med 239(4):436–441

    CAS  Google Scholar 

  • Joshi SV, Vyas BA, Shah PD, Shah DR, Shah SA, Gandhi TR (2011) Protective effect of aqueous extract of Oroxylum indicum Linn (root bark) against DNBS-induced colitis in rats. Indian J Pharmacol 43(6):656

    PubMed Central  PubMed  Google Scholar 

  • Jurjus AR, Khoury NN, Reimund JM (2004) Animal models of inflammatory bowel disease. J Pharmacol Toxicol Methods 50:81–92

    CAS  PubMed  Google Scholar 

  • Kamada N, Seo SU, Chen GY, Núñez G (2013) Role of the gut microbiota in immunity and inflammatory disease. Nat RevImmunol 13(5):321–335

    CAS  Google Scholar 

  • Kaneko A, Kono T, Miura N, Tsuchiya N, Yamamoto M (2013) Preventive effect of TU-100 on a Type-2 model of colitis in mice: possible involvement of enhancing adrenomedullin in intestinal epithelial cells. Gastroenterol Res Pract. doi:10.1155/2013/384057

  • Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EES, Higgins DE, Schreiber S, Glimcher LH et al (2008) XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134:743–756

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kawada M, Arihiro A, Mizoguchi E (2007) Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease. World J Gastroentero 13(42):5581

    CAS  Google Scholar 

  • Kawamura T, Kanai T, Dohi T, Uraushihara K, Totsuka T, Iiyama R, Taneda C, Yamazaki M, Nakamura T, Higuchi T et al (2004) Ectopic CD40 ligand expression on B cells triggers intestinal inflammation. J Immunol 172:6388–6397

    CAS  PubMed  Google Scholar 

  • Kenet G, Wardi J, Avni Y, Aeed H, Shirin H, Zaidel L, Hershkoviz R, Bruck R (2001) Amelioration of experimental colitis by thalidomide. Isr Med Assoc J 3(9):644–648

    CAS  PubMed  Google Scholar 

  • Kim YJ, Kim EH, Hahm KB (2012) Oxidative stress in inflammation-based gastrointestinal tract diseases: challenges and opportunities. J Gastroen Hepatol 27(6):1004–1010

    CAS  Google Scholar 

  • Ko JK, Lam FY, Cheung AP (2005) Amelioration of experimental colitis by Astragalus membranaceus through anti-oxidation and inhibition of adhesion molecule synthesis. World J Gastroentero 11:5787–5794

    Google Scholar 

  • Kontoyiannis D, Boulougouris G, Manoloukos M, Armaka M, Apostolaki M, Pizarro T, Kotlyarov A, Forster I, Flavell R, Gaestel M, Tsichlis P, Cominelli F, Kollias G (2002) Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn’s-like inflammatory bowel disease. J Exp Med 196:1563–1574

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kremer B, Mariman R, Erk MV, Lagerweij T, Nagelkerken L (2012) Temporal colonic gene expression profiling in the recurrent colitis model identifies early and chronic inflammatory processes. PLoS ONE 7(11):e50388

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kruidenier L, Verspaget HW (2002) Oxidative stress as a pathogenic factor in inflammatory bowel disease—radicals or ridiculous? Aliment Pharmacol Ther 16(12):1997–2015

    CAS  PubMed  Google Scholar 

  • Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S (1993) Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci U S A 90:770–774

    CAS  PubMed Central  PubMed  Google Scholar 

  • Laroui H, Ingersoll SA, Liu HC, Baker MT, Ayyadurai S, Charania MA, Laroui F, Yan Y, Sitaraman SV, Merlin D (2012) Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon. PLoS ONE 7(3):e32084

    CAS  PubMed Central  PubMed  Google Scholar 

  • Leach MW, Bean AG, Mauze S, Coffman RL, Powrie F (1996) Inflammatory bowel disease in C.B-17 acid mice reconstituted with the CD45RB high subset of CD4+ T cells. Am J Pathol 148(5):1503–1515

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A (2000) Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 289:2350–2354

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lees CW, Barrett JC, Parkes M, Satsangi J (2011) New IBD genetics: common pathways with other diseases. Gut 60:1739–1753

    CAS  PubMed  Google Scholar 

  • Low D, Nguyen DD, Mizoguchi EM (2013a) Animal models of ulcerative colitis and their application in drug research. Drug Des Devel Ther 7:1341–1357

    PubMed Central  PubMed  Google Scholar 

  • Low D, Tran HT, Lee IA et al (2013b) Chitin-binding domains of Escherichia coli chiA mediates interactions with intestinal epithelial cells in mice with colitis. Gastroenterology 145(3):602–612

    CAS  PubMed  Google Scholar 

  • Mariman R, Kremer B, Erk MV, Lagerweij T, Koning F, Nagelkerken L (2012) Gene expression profiling identifies mechanisms of protection to recurrent trinitrobenzene sulfonic acid colitis mediated by probiotics. Inflamm Bowel Dis 18(8):1424–1433

    PubMed  Google Scholar 

  • Marshall B, Swain S (2011) Cytotoxic CD4 T cells in antiviral immunity. J Biomed Biotechnol. doi:10.1155/2011/954602

    PubMed Central  PubMed  Google Scholar 

  • Matsumoto S, Okabe Y, Setoyama H, Takayama K, Ohtsuka J (1998) Inflammatory bowel disease-like enteritis and caecitis in a senescence accelerated mouse P1/Yit strain. Gut 43(1):71–78

    CAS  PubMed Central  PubMed  Google Scholar 

  • McGuckin MA, Eri R, Simms LA, Florin TH, Radford-Smith G (2009) Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis 15(1):100–113

    PubMed  Google Scholar 

  • Michelle EA, Borm GB et al (2004) Animal models of inflammatory bowel disease. Drug Discov Today Dis Models 1:437–444

    Google Scholar 

  • Mitrovic M, Shahbazian A, Bock E, Pabst MA, Holzer P (2010) Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels. Br J Pharmacol 160(6):1430–1442

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mizoguchi E (2006) Chitinase 3-like-1 exacerbates intestinal inflammation by enhancing bacterial adhesion and invasion in colonic epithelial cells. Gastroenterology 130(2):398–411

    CAS  PubMed  Google Scholar 

  • Modi HK, Shrimanker MV, Patel KP, Bhadani SM (2012) A review on: screening models of inflammatory bowel disease. J Global Pharma Technol 7(4):01–09

    Google Scholar 

  • Mombaerts P, Mizoguchi E, Grusby MJ, Glimcher LH, Bhan AK, Tonegawa S (1993) Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75:274–282

    CAS  PubMed  Google Scholar 

  • Monteleone I, Vavassori P, Biancone L, Monteleone G, Pallone F (2002) Immunoregulation in the gut: success and failures in human disease. Gut 50(3):iii60–iii64

    CAS  PubMed Central  PubMed  Google Scholar 

  • Motavallian-Naeini A, Andalib S, Rabbani M, Mahzouni P, Afsharipour M, Minaiyan M (2012) Validation and optimization of experimental colitis induction in rats using 2, 4, 6-trinitrobenzene sulfonic acid. Res Pharmaceut Sci 7(3):159–169

    CAS  Google Scholar 

  • Nagatani K, Wang S, Llado V et al (2012) Chitin microparticles for the control of intestinal inflammation. Inflamm Bowel Dis 18(9):1698–1710

    PubMed Central  PubMed  Google Scholar 

  • Nakao KI, Ro A, Kibayashi K (2014) Evaluation of the morphological changes of gastric mucosa induced by a low concentration of acetic acid using a rat model. J Forensic Leg Med 22:99–106

    PubMed  Google Scholar 

  • Nenci A, Becker C, Wullaert A, Gareus R, van Loo G, Danese S, Huth M, Nikolaev A, Neufert C, Madison B et al (2007) Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446:557–561

    CAS  PubMed  Google Scholar 

  • Niu X, Fan T, Li W, Huang H, Zhang Y, Xing W (2013) Protective effect of sanguinarine against acetic acid-induced ulcerative colitis in mice. Toxicol Appl Pharm 267(3):256–265

    CAS  Google Scholar 

  • Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G (2001) Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem 276:4812–4818

    CAS  PubMed  Google Scholar 

  • Onizawa M, Nagaishi T, Kanai T, Nagano K, Oshima S, Nemoto Y, Yoshioka A, Totsuka T, Okamoto R, Nakamura T et al (2009) Signaling pathway via TNF-alpha/NF-kappaB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis. Am J Physiol Gastrointest Liver Physiol 296:G850–G859

    CAS  PubMed  Google Scholar 

  • Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ (2012) Ulcerative colitis. Lancet 380(9853):1606–1619

    PubMed  Google Scholar 

  • Owens DW, Wilson NJ, Hill AJ, Rugg EL, Porter RM, Hutcheson AM, Quinlan RA, van Heel D, Parkes M, Jewell DP, Campbell SS, Ghosh S, Satsangi J, Lane EB (2004) Human keratin 8 mutations that disturb filament assembly observed in inflammatory bowel disease patients. J Cell Sci 117:1989–1999

    CAS  PubMed  Google Scholar 

  • Panwala CM, Jones JC, Viney JL (1998) A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J Immunol 161:5733–5744

    CAS  PubMed  Google Scholar 

  • Papanikolaou I, Psilopoulos D, Liatsos Ch, Lazaris A, Petraki K, Mavrogiannis Ch (2007) Salmonella colitis or inflammatory bowel disease? A case demonstrating overlapping of clinical, endoscopic and pathologic features. Ann Gastroenterol 14(1):65–69

    Google Scholar 

  • Pastorelli L, De Salvo C, Mercado JR, Vecchi M, Pizarro TT (2013) Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics. Front Immunol 4:1–22

    Google Scholar 

  • Patel SH, Rachchh MA, Jadav PD (2012) Evaluation of anti-inflammatory effect of anti-platelet agent-clopidogrel in experimentally induced inflammatory bowel disease. Indian J Pharmacol 44(6):744–748

    CAS  PubMed Central  PubMed  Google Scholar 

  • Paunovic B, Deng X, Khomenko T, Ahluwalia A, Tolstanova G, Tarnawski A, Szabo S, Sandor Z (2011) Molecular mechanisms of basic fibroblast growth factor effect on healing of ulcerative colitis in rats. J Pharm Exp Ther 339(2):430–437

    CAS  Google Scholar 

  • Pawar AT, Anap RM, Ghodasara JV, Kuchekar BS (2011) Protective effect of hydroalcoholic root extract of rubia cordifolia in indomethacin-induced enterocolitis in rats. Indian J Pharm Sci 73(2):250–253

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pedersen J, Coskun M, Soendergaard C, Salem M, Nielsen OH (2014) Inflammatory pathways of importance for management of inflammatory bowel disease. World J Gastroentero 20(1):64

    CAS  Google Scholar 

  • Perše M, Cerar A (2012) Dextran sodium sulphate colitis mouse model: traps and tricks. Biomed Res Int. doi:10.1155/2012/718617

    Google Scholar 

  • Pizarro TT, Arseneau KO, Bamias G, Cominelli F et al (2003) Mouse models for the study of Crohn’s disease. Trends Mol Med 9(5):218–222

    CAS  PubMed  Google Scholar 

  • Powrie F (1995) T cells in inflammatory bowel disease: protective and pathogenic roles. Immunity 3(2):171–174

    CAS  PubMed  Google Scholar 

  • Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL (1994) Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity 1:553–562

    CAS  PubMed  Google Scholar 

  • Reilly MT, Harris RA, Noronha A (2012) Using genetically engineered animal models in the postgenomic era to understand gene function in alcoholism. Alcohol Res 34(3):282–291

    PubMed Central  PubMed  Google Scholar 

  • Rath HC, Wilson KH, Sartor RB (1999) Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli. Infect Immun 67:2969–2974

    CAS  PubMed Central  PubMed  Google Scholar 

  • Read S, Malmström V, Powrie F (2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+) CD4 (+) regulatory cells that control intestinal inflammation. J Exp Med 192(2):295–302

    CAS  PubMed Central  PubMed  Google Scholar 

  • Riviera-Nieves J, Bamias G, Vidrich A, Marini M, Pizarro TT, McDuffie MJ, Moskaluk CA, Cohn SM, Cominelli F (2003) Emergence of perianal fistulizing disease in the SAMP1/YitFc mouse, a spontaneous model of chronic ileitis. Gastroenterology 124:972–982

    Google Scholar 

  • Rosenstiel P, Fantini M, Brautigam K, Kuhbacher T, Waetzig GH, Seegert D, Schreiber S (2003) TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Gastroenterology 124:1001–1009

    CAS  PubMed  Google Scholar 

  • Rudolph U, Finegold MJ, Rich SS, Harriman GR, Srinivasan Y, Brabet P, Boulay G, Bradley A, Birnbaumer L (1995) Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet 10:143–150

    CAS  PubMed  Google Scholar 

  • Schiechl G, Bauer B, Fuss I, Lang SA, Moser C, Ruemmele P, Rose-John S, Neurath MF, Geissler EK, Schlitt HJ, Strober W, Fichtner-Feigl S (2011) Tumor development in murine ulcerative colitis depends on MyD88 signaling of colonic F4/80+ CD11b(high)Gr1(low) macrophages. J Clin Invest 121(5):1692–1708

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shaffer AL, Shapiro-Shelef M, Iwakoshi NN, Lee AH, Qian SB, Zhao H, Yu X, Yang L, Tan BK, Rosenwald A et al (2004) XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity 21:81–93

    CAS  PubMed  Google Scholar 

  • Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D et al (1992) Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359:693–699

    CAS  PubMed Central  PubMed  Google Scholar 

  • Siegmund B, Zeitz M (2011) Innate and adaptive immunity in inflammatory bowel disease. World J Gastroentero 17(27):3178

    Google Scholar 

  • Simpson SJ, Shah S, Comiskey M, de Jong YP, Wang B, Mizoguchi E, Bhan AK, Terhorst C (1998) T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/Signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells. J Exp Med 187:1225–1234

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sotnikova R, Nosalova V, Navarova J (2013) Efficacy of quercetin derivatives in prevention of ulcerative colitis in rats. Interdiscip Toxicol 6(1):9–12

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stadnicki A, Colman RW (2003) Experimental models of inflammatory bowel disease. Arch Immunol Ther Exp 51:149–155

    Google Scholar 

  • Sugawara K, Olson TS, Moskaluk CA, Stevens BK, Hoang S, Kozaiwa K, Cominelli F, Ley KF, McDuffie M (2005) Linkage to peroxisome proliferator-activated receptor-gamma in SAMP1/YitFc mice and in human Crohn’s disease. Gastroenterology 128:351–360

    CAS  PubMed  Google Scholar 

  • Tanner SM, Staley EM, Lorenz RG (2013) Altered generation of induced regulatory T cells in the FVB.mdr1a−/− mouse model of colitis. Mucosal Immunol 6(2):309–323

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tran CD, Katsikeros R, Abimosleh SM (2012) Current and novel treatments for ulcerative colitis. In: Shennak M (ed) Ulcerative colitis from genetics to complications, InTech, ISBN: 978-953-307-853-3

  • Uhlig HH (2013) Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease. Gut 62(12):1795–1805

    CAS  PubMed  Google Scholar 

  • Unutmaz D, Pulendran B (2009) The gut feeling of Treg cells: IL-10 is the silver lining during colitis. Nat Immunol 10:1141–1143

    CAS  PubMed  Google Scholar 

  • Wallace KL, Zheng LB, Kanazawa Y, Shih DQ (2014) Immunopathology of inflammatory bowel disease. World J Gastroentero 20(1):6

    CAS  Google Scholar 

  • Wang YH, Ge B, Yang XL, Zhai J, Yang LN, Wang XX, Liu X, Shi JC, Wu YJ (2011) Proanthocyanidins from grape seeds modulates the nuclear factor-kappa B signal transduction pathways in rats with TNBS-induced recurrent ulcerative colitis. Int Immunopharmacol 11(10):1620–1627

    CAS  PubMed  Google Scholar 

  • Watanabe M, Ueno Y, Yajima T et al (1998) Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa. J Exp Med 187(3):389–402

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wilk JN, Bilsborough J, Viney JL (2005) The mdr1a−/− mouse model of spontaneous colitis: a relevant and appropriate animal model to study inflammatory bowel disease. Immunol Res 31:151–159

    CAS  PubMed  Google Scholar 

  • Wirtz S, Neurath MF (2007) Mouse models of inflammatory bowel disease. Adv Drug Deliver Rev 59:1073–1083

    CAS  Google Scholar 

  • Wirtz S, Finotto S, Kanzler S, Lohse AW, Blessing M, Lehr HA, Galle PR, Neurath MF (1999) Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF- plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens. J Immunol 162:1884–1888

    CAS  PubMed  Google Scholar 

  • Wirtz S, Neurath MF et al (2000) Animal models of intestinal inflammation: new insights into the molecular pathogenesis and immunotherapy of inflammatory bowel disease. Int J Colorectal Dis 15(3):144–160

    CAS  PubMed  Google Scholar 

  • Xia B, Guo HJ, Crusius JBA, Deng CS, Meuwissen SGM, Peña AS (1998) In vitro production of TNFα, IL 6 and sIL 2R in Chinese patients with ulcerative colitis. World J Gastroentero 4:252–255

    CAS  Google Scholar 

  • Yan Y (2012) Pathogenesis of inflammatory bowel diseases. In: Dr. Sami Karoui (ed) Inflammatory bowel disease—advances in pathogenesis and management. InTech. doi: 10.5772/28298ISBN: 978-953-307-891-5

  • Zhang YZ, Li YY (2014) Inflammatory bowel disease: pathogenesis. World J Gastroentero 20(1):91

    CAS  Google Scholar 

  • Zheng L, Gao ZQ, Wang SX (2000) A chronic ulcerative colitis model in rats. World J Gastroentero 6:150–152

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, I.S.F College of Pharmacy, Moga, 142001, Punjab, India

    Nidhi Goyal, Ajay Rana, Abhilasha Ahlawat, Krishna Reddy V. Bijjem & Puneet Kumar

Authors
  1. Nidhi Goyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ajay Rana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abhilasha Ahlawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Krishna Reddy V. Bijjem
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Puneet Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Puneet Kumar.

Additional information

Collection of data For this review article, literature has been surveyed thoroughly, and the references that were relevant to the study have been selected without any kind of biasing. For the collection of data, we have searched on PubMed, Google Scholar, Science Direct, Plos One, etc., and approximately 2,997 articles were obtained for animal models of IBD, while approximately 900 articles were there each for UC and CD. But only the articles that were recent and relevant to our study have been selected for the compilation of data.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Goyal, N., Rana, A., Ahlawat, A. et al. Animal models of inflammatory bowel disease: a review. Inflammopharmacol 22, 219–233 (2014). https://doi.org/10.1007/s10787-014-0207-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-014-0207-y

Keywords

Search

Navigation