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Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis.

Authors: Masterson, JC  McNamee, EN  Hosford, L  Capocelli, KE  Ruybal, J  Fillon, SA  Doyle, AD  Eltzschig, HK  Rustgi, AK  Protheroe, CA  Lee, NA  Lee, JJ  Furuta, GT 
Citation: Masterson JC, etal., Gut. 2014 Jan;63(1):43-53. doi: 10.1136/gutjnl-2012-303631. Epub 2012 Nov 17.
Pubmed: (View Article at PubMed) PMID:23161496
DOI: Full-text: DOI:10.1136/gutjnl-2012-303631

OBJECTIVE: Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition of the oesophagus with limited treatment options. No previous transgenic model has specifically targeted the oesophageal mucosa to induce oesophageal eosinophilia. DESIGN: We developed a mouse model that closely resembles EoE by utilising oxazolone haptenation in mice with transgenic overexpression of an eosinophil poietic and survival factor (interleukin (IL)-5) in resident squamous oesophageal epithelia. RESULTS: Overexpression of IL-5 in the healthy oesophagus was achieved in transgenic mice (L2-IL5) using the squamous epithelial promoter Epstein-Barr virus ED-L2. Oxazolone-challenged L2-IL5 mice developed dose-dependent pan-oesophageal eosinophilia, including eosinophil microabscess formation and degranulation as well as basal cell hyperplasia. Moreover, oesophagi expressed increased IL-13 and the eosinophil agonist chemokine eotaxin-1. Treatment of these mice with corticosteroids significantly reduced eosinophilia and epithelial inflammation. CONCLUSIONS: L2-IL5 mice provide a novel experimental model that can potentially be used in preclinical testing of EoE-related therapeutics and mechanistic studies identifying pathogenetic features associated with mucosal eosinophilia.


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CRRD Object Information
CRRD ID: 11354947
Created: 2016-07-29
Species: All species
Last Modified: 2016-07-29
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.