Leila Smith1, Solene Gatault1, Laura Casals-Diaz2, Pamela A Kelly3, Eric Camerer4, Charles Métais1, Ulla G Knaus5, Günther Eissner6, Martin Steinhoff1,7. 1. Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin 4, Ireland. 2. Skin Biology and Pharmacology, Almirall R&D Centre, Sant Feliu de Llobregat, Barcelona, Spain. 3. Department of Veterinary Pathology, School of Veterinary Medicine, University College Dublin, Dublin 4, Ireland. 4. INSERM U970, Paris Cardiovascular Research Centre, Paris, France. 5. Conway Institute, School of Medicine, University College Dublin, Dublin 4, Ireland. 6. Systems Biology Ireland, University College Dublin, Dublin 4, Ireland. 7. Department of Dermatology, Hamad Medical Corporation and Qatar University, Doha, Qatar.
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.
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 PAR2OEmice 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:PAR2OEmice 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 humanAD. 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.
Authors: Joao M Braz; Todd Dembo; Alexandra Charruyer; Ruby Ghadially; Marlys S Fassett; Allan I Basbaum Journal: Proc Natl Acad Sci U S A Date: 2021-02-23 Impact factor: 11.205
Authors: Nikolett Vasas; Zsófia Pénzes; Kornél Kistamás; Péter Pál Nánási; Szabolcs Molnár; Andrea Szegedi; Attila Gábor Szöllősi; Tamás Bíró Journal: Exp Dermatol Date: 2022-02-04 Impact factor: 4.511