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Effects of Exposure of Formaldehyde to a Rat Model of Atopic Dermatitis Induced by Neonatal Capsaicin Treatment
Published on: September 27, 2017
House dust mite-treated PAR2 over-expressor mouse: A novel model of atopic dermatitis
Leila Smith1, Solene Gatault1, Laura Casals-Diaz2
1Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin 4, Ireland.
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.
Insights
The protease-activated receptor 2 over-expressor mouse (PAR2OE) model with house dust mite (HDM) application effectively mimics human atopic dermatitis (AD) symptoms and pathophysiology. This enhanced model offers improved reproducibility for studying AD and potential treatments.
Area of Science:
- Dermatology
- Immunology
- Genetics
Background:
- Atopic dermatitis (AD) is a complex skin condition with both intrinsic and extrinsic causes.
- Existing murine models often fail to fully represent AD's multifaceted nature.
- This study addresses the need for a more comprehensive animal model of AD.
Purpose of the Study:
- To evaluate the protease-activated receptor 2 over-expressor (PAR2OE) mouse model with topical house dust mite (HDM) application.
- To determine if this model offers a more clinically representative and comprehensive representation of atopic dermatitis.
- To assess its utility for studying AD pathophysiology and therapeutic strategies.
Main Methods:
- PAR2OE mice and control groups were treated with HDM extract.
- Evaluated clinical AD scoring, itching behavior, skin morphology, barrier function (transepidermal water loss), immune cell infiltration (hematoxylin and eosin, immunofluorescence), and inflammatory markers.
- Assessed AD-related gene expression using quantitative RT-PCR.
Main Results:
- PAR2OE mice treated with HDM exhibited characteristic AD symptoms: erythema, dryness, edema, and inflammation.
- Significant mast cell and eosinophil infiltration was observed in the dermis.
- Gene expression patterns in these mice closely mirrored those found in human AD.
Conclusions:
- The PAR2OE + HDM mouse model demonstrates classic AD pathophysiology.
- This model offers high reproducibility and comprehensive disease representation.
- It is a valuable tool for investigating atopic dermatitis and potential therapeutic interventions.
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