Experimental mouse models of allergic asthma offer new possibilities for studying disease pathogenesis and developing new therapeutics. These models are well suited to measuring factors governing the allergic immune response, airway inflammation, and pulmonary pathophysiology.
Asthma is a major cause of morbidity and mortality, affecting some 300 million people throughout the world.1 More than 8% of the US population has asthma, with the prevalence increasing.2 As with other diseases, animal models of allergic airway disease greatly facilitate understanding of the underlying pathophysiology, help identify potential therapeutic targets, and allow preclinical testing of possible new therapies. Models of allergic airway disease have been developed in several animal species, but murine models are particularly attractive due to the low cost, ready availability, and well-characterized immune systems of these animals.3 Availability of a variety of transgenic strains further increases the attractiveness of these models.4 Here we describe two murine models of allergic airway disease, both employing ovalbumin as the antigen. Following initial sensitization by intraperitoneal injection, one model delivers the antigen challenge by nebulization, the other by intratracheal delivery. These two models offer complementary advantages, with each mimicking the major features of human asthma.5
The major features of acute asthma include an exaggerated airway response to stimuli such as methacholine (airway hyperresponsiveness; AHR) and eosinophil-rich airway inflammation. These are also prominent effects of allergen challenge in our murine models,5,6 and we describe techniques for measuring them and thus evaluating the effects of experimental manipulation. Specifically, we describe both invasive7 and non-invasive8 techniques for measuring airway hyperresponsiveness as well as methods for assessing infiltration of inflammatory cells into the airways and the lung. Airway inflammatory cells are collected by bronchoalveolar lavage while lung histopathology is used to assess markers of inflammation throughout the organ. These techniques provide powerful tools for studying asthma in ways that would not be possible in humans.
Animal models of allergic airway disease provide important tools for studies relevant to clinical asthma. A number of different models, employing varying species and antigens, have been developed. The mouse, an attractive and frequently used laboratory species, also offers a number of advantages for models of allergic airway disease.9,10 Although such models do not mimic asthma in every respect,11 with aspects of chronic disease being particularly difficult to reproduce,12,13 we confirm h…
The authors have nothing to disclose.
This work was supported by NIH Grant HL093196 (R.C.R.) and the Atlanta Research and Education Foundation (AREF).
Material Name | Company | Catalogue Number | Comments |
Ovalbumin | Sigma-Aldrich St. Louis, MO |
A5503 | |
Aluminum hydroxide | Sigma-Aldrich | 239186 | |
Acetyl-β-methylcholine chloride | Sigma-Aldrich | A2251 | |
Pentobarbital sodium salt | Sigma-Aldrich | P3761 | |
Whole body plethysmography (WBP) system |
Buxco Research Systems Wilmington, NC |
http://www.buxco.com | |
FlexiVent | SCIREQ, Inc. Montreal, Canada |
http://www.scireq.com | |
Light microscope | Leica Microsystems, Inc. Buffalo Grove, IL |
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Cytospin 4 | Thermo Scientific Asheville, NC |
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Diff-Quick stain | Siemens Newark, DE |
B4132-1A | |
Repetitive pipette | Tridak Torrington, CT |
STP4001-0025 |