Mouse models to evaluate the function of genes associated with allergic airway disease

Abstract

In recent years, considerable effort has been invested in developing mouse models of allergic airway disease, as a means of evaluating the role of select genes in its pathophysiology. Here, we review the principal models used in this field, including models of allergic asthma and hypersensitivity pneumonitis. As an example of how these models can reveal novel functional roles for genes, we review our work showing a role for the stem-cell-associated gene, Cd34. Through this example, we illustrate the genetic and immunological strategies available in the field to better understand allergic airway inflammation. CD34 was found to play an important role in the development of two different models of allergic disease, that is, Th2-driven allergic asthma and Th17-driven hypersensitivity pneumonitis. Using a combination of genetically modified mice as well as cell transfers and chimeric mice, we showed that CD34 is important for the efficient trafficking of hematopoietic subsets into and out of the lung, including mast cells, eosinophils and dendritic cells. The currently available array of mutant mice and animal models of allergic disease now offers an opportunity to make profound insights into these diseases and provide preclinical models for the development of therapeutics.