Alcohol-induced behavior change in zebrafish models. Would you like email updates of new search results? doi:10.1089/zeb.2013.0917, 31. Thus, IAP is involved in the protecting the intestine from microbe-related lesions and is suggested that abnormal microbiota cause IBD by influencing IAP activity. Apart from toxicity studies, another major application of zebrafish is to serve as an animal model for drug discovery , especially the in vivo evaluation of engineered nanomedicines. Brugman et al. Temporal electron microscopy analyses demonstrated that PI-deficient intestinal epithelium cells undergo chronic ER stress-mediated cytopathology, including disruption of the ER and Golgi apparatus, mitochondrial damage, autophagy, and apoptosis. Another compound leflunomide has also been approved in clinical trial to cure melanoma in combination with vemurafenib. Controversy concerning the etiology of IBD exists because of its multifactorial pathogenesis. The effect of certain chemicals can be analyzed in a specific biological system, and small molecules are then used to disturb the biological processes directly. HEG1, a heart development protein with EGF like domains 1, plays important roles in the development of vertebrate cardiovascular system. Inflamm Bowel Dis (2006) 12(Suppl 1):S3–9. Nature (2013) 496:494–7. With zebrafish models, we can easily incorporate sophisticated preclinical screenings during the nanoscale delivery system development [13,23,24,30–32,34,38,44]. 2003 Mar;6(2):218-23. Wallace KN, Akhter S, Smith EM, Lorent K, Pack M. Intestinal growth and differentiation in zebrafish. This work was supported by the National Natural Science Foundation of China (grant number 8147082). In addition to studies in genetics and developmental biology, zebrafish has also been widely used in human disease modeling and drug screening. Hence, immune responses can be traced in vivo in a complete organism. Int J Med Microbiol (2016) 306:302–9. Oehlers SH, Flores MV, Hall CJ, Crosier KE, Crosier PS. J Comp Neurol (2007) 505:235–48. Zoller M. Gastrointestinal tumors: metastasis and tetraspanins. The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model. Abundant neutrophils are observed under LPS exposure, while neutrophils are insufficient in the GF IAP-deficient phenotype. Both of these factors lead to an abnormal chronic or recurring immune response, resulting in tissue injury with ulceration and bowel inflammation (2). We also review the progress and deficiencies of the zebrafish model for scientific applications. doi:10.1152/ajpgi.90534.2008, 6. doi:10.1038/sj.embor.7400638, 14. Compared with the pure chemical model, chemical genetic methods have a more widespread application in drug screening. Applications de Zebrafish dans la recherche. Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection. Despite some limitations, zebrafish are superior to the existing models of intestinal inflammation. Nat Rev Genet (2007) 8:353–67. These two studies clearly illustrated the feasibility of using zebrafish to study the barrier function in IBD. Surprisingly, the expression of CXCL8 is significantly enhanced in the larval intestine of TNBS-induced enterocolitis zebrafish models (49). Cheesman et al. There was a lack of brush border intestinal alkaline phosphate (IAP) activity and glycan expression was immature. Identification and characterization of the familial adenomatous polyposis coli gene. Nat Rev Immunol (2013) 13:321–35. Besides, researches of the stem cells located at the base of the crypt of mammalian intestinal epithelium are heating up in recent years (94). This high similarity, and a clearer understanding of the critical genomic features, could promote the identification of susceptibility genes of IBD (11). One might also consider forward- and. Goldsmith JR, Cocchiaro JL, Rawls JF, Jobin C. Glafenine-induced intestinal injury in zebrafish is ameliorated by mu-opioid signaling via enhancement of Atf6-dependent cellular stress responses. FIGURE 4 Response to antiepileptic drugs. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Development (2013) 140:4445–51. A systematic genome-wide analysis of zebrafish protein-coding gene function. doi:10.1038/nature12972, Keywords: zebrafish, inflammatory bowel disease, murine model, pathogenesis, drug screening, Citation: Hanyang L, Xuanzhe L, Xuyang C, Yujia Q, Jiarong F, Jun S and Zhihua R (2017) Application of Zebrafish Models in Inflammatory Bowel Disease. Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia. With the assistance of newly developed strains, and high-throughput genetic and chemical screens, investigators are able to clarify the suppressors and the enhancers of inflammation (32). Oxazolone upregulated the expression of a series of genes encoding colitis-related cytokines, including pro-inflammatory (i.e., IL-1β, TNF-α) and anti-inflammatory cytokines (i.e., IL-10) in the intestine. In addition to the well-known pro-inflammatory and anti-inflammatory cytokines, inflammation-related factors and signaling pathway might also be associated with the pathogenesis of IBD. Duplicated genes are one of the essential parts of the zebrafish genome, which indicates that homologs of mammal immune factors might not have conserved functions in zebrafish. In developmental biology, fluorescence-activated cell sorting is combined with microarray profiling to identify genes and proteins involved in the intestinal development (89). doi:10.1016/0016-5085(92)91710-L, 24. Agents and chemical models cause non-specific intestinal defects. 2008 Oct-Nov;98(2-3):301-8. doi: 10.1016/j.pbiomolbio.2009.01.011. However, the pathogenesis and etiology of IBD remain incompletely understood. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Cell (2008) 134:743–56. Genes containing a putative transcription factor binding sequence, GGAANCGGAANY and a nucleolar gene network were identified in novel pathways, such as the PI3 signaling and inositol metabolism pathway, by activating the key mediator AKT2 (89). Zebrafish as tools for drug discovery. Investigators have used IBD animal models for over 100 years, from drug-induced methods to genetic engineering models (20). These heterozygous mutations were confirmed to have a relationship with truncated forms of adenomatous polyposis coli (APC). doi:10.1007/s40139-015-0079-x, 8. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Studies in experimental animals have indicated that the intestinal microbiota play a critical role in the pathogenesis of intestinal inflammation (80). For example, retinoic acid can suppress both basal and intestinal mucus production; thus exacerbating experimental enterocolitis in the zebrafish model (50). doi:10.1002/ibd.22929, 61. Adolph TE, Tomczak MF, Niederreiter L, Ko HJ, Bock J, Martinez-Naves E, et al. For example, human CXCL8 regulates the chemotaxis of neutrophils. doi:10.1038/nrgastro.2015.72, 39. The pathogenesis of IBD is still unclear and many risk factors remain unidentified. Brugman S, Liu KY, Lindenbergh-Kortleve D, Samsom JN, Furuta GT, Renshaw SA, et al. Mokry M, Middendorp S, Wiegerinck CL, Witte M, Teunissen H, Meddens CA, et al. The pathogenesis of IBD is still unclear and many risk factors remain unidentified. doi:10.1002/eji.201040899, 41. The cdipthi559 zebrafish mutant has a deficiency in PI synthesis and shows characteristics of ER stress in the intestinal epithelium (39). IKK refers to inhibitor of nuclear factor kappa-B (NF-κB) kinase, which participates in the cellular immune response caused by cytokines. Intrarectal ethanol administration (20%) resulted in reduced survival, upregulated infiltration and proliferation of immune cells, and prolonged inflammatory cytokine responses in some MSP-deficient zebrafish (44). According to current evidence, zebrafish have orthologs of mammalian toll-like receptors (TLRs), which are the innate immune receptors that recognize specific microbial molecules (29), and have functionally conserved orthologs of human IBD susceptibility genes NOD1 and NOD2 (11). Hence, such a model could be used to study adaptive immunity in IBD pathogenesis. Zebrafish are highly fecund: a female lays hundreds of eggs each time with a generation time of approximately 3–4 months and the eggs can be fertilized in vitro. Surprisingly, the expressions of downstream proteins ATF6 and s-XBP1 did not increase, explaining the impaired UPR. Zebrafish are also amenable to manipulation of brain activity: optog… doi:10.1002/ibd.20129, 66. These approaches have provided a better view of the pathogenesis of IBD, which will be discussed in detail in the following section. Glocker EO, Kotlarz D, Boztug K, Gertz EM, Schaffer AA, Noyan F, et al. EMBO Rep (2006) 7:444–9. In this review, we compare traditional murine models and zebrafish models in terms of advantages, pathogenesis, and drug discovery screening for IBD. The improvement in genetic manipulation techniques for forward genetics has permitted the identification of over 160 IBD susceptibility genes in the human genome, most of which are associated with autophagy, host responses to bacteria, and the immune response: many of these have orthologs in the zebrafish genome (7, 24). Prog Biophys Mol Biol. In addition, aseptic techniques provide a convenient control of the microbial system in zebrafish (30). doi:10.1242/dmm.006122, 12. The expression of MCH and the MCH receptor were upregulated in the intestine of model of zebrafish. Proc Natl Acad Sci U S A (2008) 105:10613–8. doi:10.1242/dev.101170, 19. Characterization of spontaneous colitis in cotton-top tamarins (Saguinus oedipus) and its response to sulfasalazine. 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