House dust mite (HDM) animal models
Often we receive questions about house dust mite animal models. Which models are researchers using, which model do we recommend, what are the differences? To answer these questions we have contacted multiple research institutes all over the world and collected their models and background information. On this page a selection of these models.
Overview of different HDM induced asthma models
Multiple research groups from universities all over the world are using different murine models to test their hypothesises. In the table below you can find different known allergic asthma protocols and their results. This overview can be used as an indication for which allergic asthma protocol you can use for your research.
Click on one of the models for more information.
|1. Click for more info||Challenged with HDM by intranasal administration on days 2, 4, 6. Mice were sacrificed 24 hours after the last challenge.||7 days||Acute inflammatory model||Total and differential cell count in the BALF/Lung|
|2. Click for more info||Sensitized with HDM by intranasal administration on day 0, followed by intranasal challenge at days 6, 7, 8, 9, 10. Mice were sacrificed 3 hours after the last challenge.||14 days||Acute sensitisation/ challenge model||Total and differential cell count. Inflammatory mediator content|
|3. Click for more info||Sensitized with HDM by intranasal administration on day 0, followed by intranasal challenge at days 14, 15, 16 and 17. Mice were sacrificed 3 hours after the last challenge.||17 days||Acute sensitisation/ challenge model||Total and differential cell count in the BALF/Lung|
|4. Click for more info||Challenged with HDM by intranasal administration on days 2, 4, 6, 9, 11, 13, 16,18,20. Mice were sacrificed 24 hours after the last challenge.||21 days||Acute challenge model||Airway hyper-reactivity and detailed lung mechanics; flexiVent™. Histopathology and immunohistochemistry. Total and differential cell count in the BALF/Lung.|
|5. Click for more info||Sensitized with HDM by intranasal administration on days 0 and 14 followed by SCIT therapy on days 21, 23 and 25, followed by intranasal challenge at days 39, 42 and 44, performing an AHR test on day 45 and sacrificing mice at day 46||46 days||New HDM (Immuno) therapy testing||Airway hyper-reactivity and detailed lung mechanics; flexiVent™. Eosinophil cell count in the BALF. Inflammatory mediator content.|
|6. Click for more info||Sensitized with HDM by intranasal administration on days 1 and 15 followed by intranasal challenge at days 54, 56 and 58, finally taking postserum samples for analysis at day||60 days||Sensitisation/ challenge model||Airway hyper-reactivity and detailed lung mechanics; flexiVent™. Total and differential cell count in the BALF. Inflammatory mediator content.|
Clinical background allergic asthma
Allergic asthma is a life-long chronic inflammatory disorder within the airways. At severe disease structural changes and remodelling of the airway wall takes place (figure 6). Allergic asthma is a common disease among children and adults (Pawankar et al., 2011). Symptoms of asthma include wheezing, shortness of breath, coughing (especially at night), less energy and chest tightness, pain or pressure (Longfonds, 2015). Asthma is associated with airflow obstruction and hyper responsiveness which is most of the time reversible. In some cases medication is needed to reverse the effects. Corticosteroids which need to be inhaled are currently the most effective treatment. The highest identifiable susceptible factor to develop asthma is atopy. Atopy is a genetic marker to develop IgE mediated sensitivity to allergens. Quality of life can get worse for patients with asthma. Asthma is a serious public health problem in the entire world, especially in middle and low income countries. The problem with asthma is that there is no curing therapy yet on the market and there is no worldwide control (Pawankar et al., 2011).
The basic molecular and cellular mechanisms of acute airway inflammation and allergic sensitization are largely revealed by animal models, the knowledge about implications and mechanisms of remodelling and chronic airway inflammation is still missing. The complex nature of allergic asthma results in that not one single animal model includes all the different aspects of childhood and adult asthma. Therefore, different allergic asthma animal models are used to get an optimal understanding of the process of asthma and drug testing. All research institutes strive to optimize effective and clinically translatable outcomes.
Although murine models have been useful in understanding the basic cellular and molecular mechanisms of allergic sensitization and acute airway inflammation, they have generally been much less productive in advancing our understanding of the mechanisms and implications of chronic airway inflammation and remodelling.
Ovalbumin in allergic asthma models
The antigen generally used in the allergic asthma models is ovalbumin (abbreviated OVA) is the main protein found in egg white, making up approximately 55% of the total protein. Ovalbumin displays sequence and three-dimensional homology to the serpin superfamily, but unlike most serpins it is not a serine protease inhibitor. The function of ovalbumin is unknown, although it is presumed to be a storage protein. OVA is commonly used to stimulate an allergic reaction in test subjects, e.g. established model allergen for airway hyper-responsiveness (AHR), but it is not a common environmental aeroallergen. Respiratory exposure to OVA results in inhalation tolerance. Continuous exposure to OVA in a sensitized animal leads to a diminution, in fact a complete abrogation, of airway inflammation. Concluding that respiratory exposure to OVA does not lead to chronic airway inflammation.
Whereas the surrogate allergen ovalbumin has been extremely valuable for unraveling underlying mechanisms of the disease, murine asthma models depend nowadays on naturally occurring allergens. On this page we describe the relevant models of acute allergic asthma based on sensitization and challenge with HDM extracts.
The use of house dust mites in allergic asthma models
The best way to optimize the allergic asthma model is the use of common environmental aeroallergens. The two most common environmental aeroallergens are house dust mites (HDM) and ragweed.
The study of Johnson et al.(2004) investigated the impact of prolonged exposure, regarding 5 to 7 weeks, to a house dust mite extract on local and systemic immuno-inflammatory responses. They also investigated the effects of the structural and functional consequences of such exposure. Their results showed that chronic exposure to HDM extract led to a prominent and sustained airway eosinophilic inflammation. Elevated serum levels of helper T cell type 2 (Th2) associated immunoglobulins and significantly increased production of Th2 associated cytokines by splenocytes in-vitro was also observed. In the lung a continual accumulation of activated/effector T cell subsets was found. Evidence of goblet cell hyperplasia, significant increases in sub epithelial collagen deposition and contractile tissue was observed. After five weeks of HDM extract exposure the airway reactivity to methacholine was noticeably increased. Persistent functional and structural abnormalities were observed even after nine weeks of non-exposure. Concluding that running the allergic asthma model with HDM extract mimics the situation of the patient better than running the model with ovalbumin. This model was ran in female balb/c mice of 6-8 weeks old.
All allergic asthma models
- Acute inflammatory model (7 days)
- Acute sensitization/ challenge model (14 days)
- Acute sensitization/ challenge model (17 days)
- Acute challenge model (21 days)
- New HDM (immuno)therapy testing (45 days)
- Sensitization/ challenge model (60 days)
Our HDM extracts
- Johnson et al. (2004). Continuous Exposure to House Dust Mite Elicits Chronic Airway Inflammation and Structural Remodeling. American Journal of Respiratory and Critical Care Medicine, pp 378–385,.
- American Academy of Allergy, A. &. (2016). Asthma Statistics. Opgeroepen op 1 18, 2016, van American Academy of Allergy, Asthma & Immunology: http://www.aaaai.org/about-the-aaaai/newsroom/asthma-statistics.aspx
- Longfonds. (2015). Symptomen van astma. Opgeroepen op 01 28, 2016, van Longfonds: https://www.longfonds.nl/astma/alles-over-astma/symptomen-astma?gclid=COnD0_GTzMoCFUWNGwodm7cAyQ
- Pawankar et al., R. (2011). WAO White Book on Allergy. United States of America: World Allergy Organization.
- WAO, W. A. (2011). White Book on Allergy. Wisconsin: World Allergy Organization.