PUBLICATION
A chemical enterocolitis model in zebrafish larvae that is dependent on microbiota and responsive to pharmacological agents
- Authors
- Oehlers, S.H., Flores, M.V., Okuda, K.S., Hall, C.J., Crosier, K.E., and Crosier, P.S.
- ID
- ZDB-PUB-110103-13
- Date
- 2011
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 240(1): 288-298 (Journal)
- Registered Authors
- Crosier, Kathy, Crosier, Phil, Flores, Maria, Hall, Chris, Oehlers, Stefan, Okuda, Kazuhide Shaun
- Keywords
- drug discovery, inflammation, leukocytes, microbiota, Zebrafish
- MeSH Terms
-
- Animals
- Anti-Inflammatory Agents/pharmacology
- Anti-Inflammatory Agents/therapeutic use*
- Disease Models, Animal*
- Embryo, Nonmammalian
- Enterocolitis/chemically induced
- Enterocolitis/microbiology*
- Enterocolitis/pathology
- Enterocolitis/prevention & control*
- Gastrointestinal Tract/blood supply
- Gastrointestinal Tract/drug effects
- Gastrointestinal Tract/microbiology*
- Gastrointestinal Tract/pathology
- Haptens/immunology
- Haptens/metabolism
- Humans
- Larva
- Leukocytes/drug effects
- Leukocytes/metabolism
- Leukocytes/pathology
- Metagenome/physiology*
- Myeloid Differentiation Factor 88/genetics
- Myeloid Differentiation Factor 88/metabolism
- Myeloid Differentiation Factor 88/physiology
- Trinitrobenzenesulfonic Acid
- Zebrafish*/embryology
- Zebrafish*/growth & development
- PubMed
- 21181946 Full text @ Dev. Dyn.
Citation
Oehlers, S.H., Flores, M.V., Okuda, K.S., Hall, C.J., Crosier, K.E., and Crosier, P.S. (2011) A chemical enterocolitis model in zebrafish larvae that is dependent on microbiota and responsive to pharmacological agents. Developmental Dynamics : an official publication of the American Association of Anatomists. 240(1):288-298.
Abstract
Inflammatory bowel disease (IBD) results from dysfunctional interactions between the intestinal immune system and microbiota, influenced by host genetic susceptibility. Because a key feature of the pathology is intestinal epithelial damage, potential disease factors have been traditionally analyzed within the background of chemical colitis models in mice. The zebrafish has greatly complemented the mouse for modeling aspects of disease processes, with an advantage for high content drug screens. Larval zebrafish exposed to the haptenizing agent trinitrobenzene sulfonic acid (TNBS) displayed impaired intestinal homeostasis and inflammation reminiscent of human IBD. There was a marked induction of pro-inflammatory cytokines, the degradative enzyme mmp9 and leukocytosis. Enterocolitis was dependent on microbiota and Toll-like receptor signaling, that can be ameliorated by antibiotic and anti-inflammatory drug treatments. This system will be useful to rapidly interrogate in vivo the biological significance of the IBD candidate genes so far identified and to carry out pharmacological modifier screens.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping