MOUSE MODELS OF AIRWAY RESPONSIVENESS: Physiological Basis of Observed Outcomes and Analysis of Selected Examples Using These Outcome Indicators

The mouse is an ideal species for investigation at the interface of lung biology and lung function. As detailed in this review, there are well-developed methods for the quantitative study of lung function in mice. These methods can be applied to mice in both terminal and nonterminal experiments. Terminal experimental approaches provide more detailed physiological information, but nonterminal measurements provide adequate data for certain experiments. In this review, we provide two examples of how these models can be used to further understanding of the primary pathobiology of airway responsiveness in both the absence and the presence of induced airway inflammation. The first model is a dissection of chromosomal loci linked to the variance in airway responsiveness observed in the absence of any manipulation to induce airway inflammation. The second model explores the role of T-cell costimulatory signals in the induction of airway hyperresponsiveness. As the number of mice with targeted deletions of effector genes or insertion of informative transgenes grows, additional examples are likely to accrue.