House dust mite-treated PAR2 over-expressor mouse: A novel model of atopic dermatitis

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Title: House dust mite-treated PAR2 over-expressor mouse: A novel model of atopic dermatitis
Authors: Smith, LeilaGatault, SolèneCasals-Diaz, LauraKelly, Pamela A.Camerer, EricMétais, CharlesKnaus, Ulla G.Eissner, GüntherSteinhoff, Martin
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Date: Nov-2019
Online since: 2021-02-03T16:20:10Z
Abstract: Background: Atopic dermatitis (AD) is a complex skin disease involving causative effects from both intrinsic and extrinsic sources. Murine models of the disease often fall short in one of these components and, as a result, do not fully encapsulate these disease mechanisms. Objective: We aimed to determine whether the protease-activated receptor 2 over-expressor mouse (PAR2OE) with topical house dust mite (HDM) application is a more comprehensive and clinically representative AD model. Methods: Following HDM extract application to PAR2OE mice and controls, AD clinical scoring, itching behaviour, skin morphology and structure, barrier function, immune cell infiltration and inflammatory markers were assessed. Skin morphology was analysed using haematoxylin and eosin staining, and barrier function was assessed by transepidermal water loss measurements. Immune infiltrate was characterised by histological and immunofluorescence staining. Finally, an assessment of AD-related gene expression was performed using quantitative RT-PCR. Results: PAR2OE mice treated with HDM displays all the characteristic clinical symptoms including erythema, dryness and oedema, skin morphology, itch and inflammation typically seen in patients with AD. There is a significant influx of mast cells (P <.01) and eosinophils (P <.0001) into the dermis of these mice. Furthermore, the PAR2OE + HDM mice exhibit similar expression patterns of key differentially expressed genes as seen in human AD. Conclusion: The PAR2OE + HDM mouse presents with a classic AD pathophysiology and is a valuable model in terms of reproducibility and overall disease representation to study the condition and potential therapeutic approaches.
Funding Details: Science Foundation Ireland
Funding Details: French National Research Agency
Type of material: Journal Article
Publisher: Wiley
Journal: Experimental Dermatology
Volume: 28
Issue: 11
Start page: 1298
End page: 1308
Copyright (published version): 2019 Wiley
Keywords: Atopic dermatitisHouse dust miteMouse modelProtease-activated receptor 2Skin barrier
DOI: 10.1111/exd.14030
Language: en
Status of Item: Peer reviewed
ISSN: 0906-6705
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Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection
Veterinary Medicine Research Collection

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