Abstract
Murine models of allergic asthma have been used to understand the mechanisms of development and pathology in this disease. In addition, knockout mice have contributed significantly to our understanding of the roles of specific molecules and cytokines in these models. However, results can vary significantly depending on the mouse strain used in the model, and in particularly in understanding the effect of specific knockouts. For example, it can be equivocal as to whether specific gene knockouts affect the susceptibility of the mice to developing the disease, or lead to resistance. Here we used a house dust mite model of allergic airway inflammation to examine the response of two strains of mice (C57BL/6 and BALB/c) which differ in their responses in allergic airway inflammation. We demonstrate an algorithm that can facilitate the understanding of the behavior of these models with regards to susceptibility (to allergic airway inflammation) (Saai) or resistance (Raai) in this model. We verify that both C57BL/6 and BALB/c develop disease, but BALB/c mice have higher Saai for development. We then use this approach to show that the absence of the Tec family kinase Itk, which regulates the production of Th2 cytokines, leads to Raai in the C57BL/6 background, but decreases Saai on the BALB/c background. We suggest that the use of such approaches could clarify the behavior of various knockout mice in modeling allergic asthma.
Highlights
Mouse models have played significant roles in our understanding of the immunological mechanism(s) leading to the development of allergic airway inflammation
In theoretical and empirical infectious disease models, the concept of tolerance (T) and resistance (R) has been developed [9]. This concept states that animals that are infected with a pathogen may vary in their response, which can be one of complete resistance, i.e. animals are resistant to developing symptoms of an infection
Mouse models have played significant roles in our understanding of the immunological mechanisms leading to the development of allergic airway inflammation, and are used as models of allergic asthma [2]
Summary
Mouse models have played significant roles in our understanding of the immunological mechanism(s) leading to the development of allergic airway inflammation. Various strains of mice respond differently in these models, and there are more than a few examples of gene knockouts that display contrasting phenotypes in different backgrounds [1,2] This is exemplified by the known differences in behavior between C57BL/6 and BALB/c backgrounds in models of allergic airway inflammation [3]. Animals can vary in tolerance, such that the symptoms that develop after infection can be mild, and such animals would be said to have a high tolerance, while animals that have severe symptoms would be said to have low tolerance [9] These responses do not address whether animals are susceptible, i.e. able to be infected by the pathogen, or the mechanisms behind their responses. The mechanisms can be potentially traced to the presence of robust immune responses
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