PUBLICATION

A high-throughput chemically induced inflammation assay in zebrafish

Authors
d'Alencon, C.A., Pena, O.A., Wittmann, C., Gallardo, V.E., Jones, R.A., Loosli, F., Liebel, U., Grabher, C., and Allende, M.L.
ID
ZDB-PUB-110103-3
Date
2010
Source
BMC Biology   8: 151 (Journal)
Registered Authors
Allende, Miguel L., Gallardo, Viviana, Grabher, Clemens, Loosli, Felix, Wittmann, Christine
Keywords
none
MeSH Terms
  • Inflammation/chemically induced*
  • Inflammation/immunology
  • Immunologic Factors/adverse effects
  • Immunologic Factors/isolation & purification*
  • Immunologic Factors/pharmacology*
  • Leukocytes/physiology
  • Disease Models, Animal
  • Animals
  • Cell Movement/drug effects
  • Anti-Inflammatory Agents/pharmacology
  • Embryo, Nonmammalian
  • High-Throughput Screening Assays
  • Animals, Genetically Modified
  • Models, Biological
  • Reactive Oxygen Species/metabolism
  • Drug Evaluation, Preclinical/methods
  • Neutrophil Infiltration/drug effects
  • Zebrafish/immunology*
(all 18)
PubMed
21176202 Full text @ BMC Biol.
CTD
21176202
Abstract
BACKGROUND: Studies on innate immunity have benefited from the introduction of zebrafish as a model system. Transgenic fish expressing fluorescent proteins in leukocyte populations allow direct, quantitative visualization of an inflammatory response in vivo. It has been proposed that this animal model can be used for high-throughput screens aimed at the identification of novel immuno-modulatory lead compounds. However, current assays require invasive manipulation of fish individually, thus preventing high content screening. RESULTS: Here, we show that specific, non-invasive damage to lateral line neuromast cells can induce a robust acute inflammatory response. Exposure of fish larvae to sub-lethal concentrations of copper sulfate selectively damages the sensory hair cell population inducing infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be assayed in real-time using transgenic fish expressing fluorescent proteins in leukocytes or by histochemical assays in fixed larvae. We demonstrate the usefulness of this method for chemical and genetic screens to detect the effect of immuno-modulatory compounds and mutations affecting the leukocyte response. Moreover, we transformed the assay into a high-throughput screening method by using a customized automated imaging and processing system that quantifies the magnitude of the inflammatory reaction. CONCLUSIONS: This approach allows rapid screening of thousands of compounds or mutagenized zebrafish for effects on inflammation and enables the identification of novel players in the regulation of innate immunity and potential lead compounds towards new immuno-modulatory therapies. We have called this method the Chemically-Induced Inflammation Assay, or ChIn Assay. See Commentary article: http://www.biomedcentral.com/1741-7007/8/148.
Genes / Markers
Figures
Figure Gallery (8 images)
Show all Figures
Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a9
    		Complex
    hu3280
      		Point Mutation
      i114TgTransgenic Insertion
        nz50TgTransgenic Insertion
          nz117TgTransgenic Insertion
            s356tTgTransgenic Insertion
              w2
                		Point Mutation
                zf106TgTransgenic Insertion
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Fish
                  Antibodies
                  Orthology
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  DsRed2EFGDsRed2
                  EGFPEFGEGFP
                  GFPEFGGFP
                  1 - 3 of 3
                  Show
                  Mapping
                  Your Input Welcome
                  We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
                  Citation
                  d'Alencon, C.A., Pena, O.A., Wittmann, C., Gallardo, V.E., Jones, R.A., Loosli, F., Liebel, U., Grabher, C., and Allende, M.L. (2010) A high-throughput chemically induced inflammation assay in zebrafish. BMC Biology. 8:151.