Zebrafish Chemical-induced Intestinal Inflammation Models

Inflammatory bowel disease (IBD) refers predominantly to two distinct diseases: Crohn's disease (CD) and ulcerative colitis (UC), which have both overlapping and unique features. The two diseases are characterized by an abnormal response by the immune system, compromising diarrhea or rectal urgency, bleeding, constipation, abdominal pain, and loss of appetite. Besides, IBD can cause many non-digestive tract complications. Parenteral complications severely affect the patients' quality of life. Treatments to control symptoms of IBD have progressed with the recent introduction of biological agents, but these remain low in efficacy. Therefore, it is importance that we extend our understanding of this disease to enable us to find more effective treatments.

The most well-established animal model in IBD is the murine model. However, in recent years, the zebrafish has become an indispensable model in the investigation of inflammatory physiology and pathology. Compared with humans, the zebrafish has a highly similar gastrointestinal system, with a pancreas, liver, gall bladder, and intestinal tract with comparable absorptive and secretory functions. Its external and transparency, fast development and its easy manipulation and maintenance, position them as an attractive and cheaper model compared to mice. Especially, the small size of the larvae and their accessibility for compound treatment has made them an attractive model for anti-inflammatory drug screening.

Figure 1. IBD drug screen by zebrafish model.

Creative Biogene, a zebrafish research company with experienced scientists and advanced technology, has developed a series of zebrafish IBD models to help reveal anti-inflammatory activities for candidate drugs. We have generated IBD animal models for over 10 years, from drug-induced methods to genetic engineering models.

Inflammation-responsive transgenic zebrafish models
Chemically induced larval IBD models

Chemical Inducer	Zebrafish Age	Characteristics
DSS	Larva (3-6 dpf)	Mucosecretory phenotype; neutrophilic infiltration microbiota - dependent; upregulation of CCl20, IL-1β, IL8, IL23, MMP9 and PCNAIL; increased proliferating cells.
TNBS	Larva (3-8 dpf)	Dose-dependent survival; loss of villi; expansion of intestinal lumen; increased number of goblet cells; upregulation of IL-1β, IL8, TNF-α, and MMP9; infiltrate of myeloid cells; increased TNF-α expression in lumen.
Glafenine	Larva (5 dpf)	Apoptosis in intestinal epithelial cells; ER stress in IECs.

Chemically induced adult IBD models

Chemical Inducer	Zebrafish Age	Characteristics
TNBS	Adult	Dose-dependent fish survival; ulcerations; disruption of the epithelial integrity; swelling, thickening and detachment of villi; no changes in goblet cells; upregulation of IL-1β, IL8 and IL10.
Oxazolone	Larva (5 dpf)	Epithelial damage; infiltration of neutrophils and eosinophils in intestine; depletion of goblet cells; upregulation of IL-1β, IL10 and TNF-α.

These zebrafish IBD models will help to determine and exploit the pathogenesis of IBD, and reversing the growth and development of IBD in patients by drug screening or via immunosuppression. We also provide a range of IBD model testing systems to promote your drug candidates from discovery to IND. Contact us today to discuss your objectives and how we can reach them.

References

Lee J A, Renshaw S A. Zebrafish screens for new colitis treatments–a bottom-up approach. The FEBS journal, 2017, 284(3): 399-401.
Hanyang L, et al. Application of zebrafish models in inflammatory bowel disease. Frontiers in immunology, 2017, 8: 501.
Fénero C I M, et al. Inflammatory diseases modelling in zebrafish. World journal of experimental medicine, 2016, 6(1): 9.

For research use only. Not intended for any clinical use.

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