Are mouse models of asthma appropriate for investigating the pathogenesis of airway hyper-responsiveness?
- 1Department of Pathology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
- 2Discipline of Microbiology and Immunology, School of Biomedical Sciences and Pharmacy, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia
Whether mouse models of chronic asthma can be used to investigate the relationship between airway inflammation/remodeling and airway hyper-responsiveness (AHR) is a vexed question. It raises issues about the extent to which such models replicate key features of the human disease. Here, we review some of the characteristic pathological features of human asthma and their relationship to AHR and examine some limitations of mouse models that are commonly used to investigate these relationships. We compare these conventional models with our mouse model of chronic asthma involving long-term low-level inhalational challenge and review studies of the relationship between inflammation/remodeling and AHR in this model and its derivatives, including models of an acute exacerbation of chronic asthma and of the induction phase of childhood asthma. We conclude that while extrapolating from studies in mouse models to AHR in humans requires cautious interpretation, such experimental work can provide significant insights into the pathogenesis of airway responsiveness and its molecular and cellular regulation.
Keywords: airway hyper-responsiveness, airway inflammation, airway remodeling, animal models, asthma
Citation: Kumar RK and Foster PS (2012) Are mouse models of asthma appropriate for investigating the pathogenesis of airway hyper-responsiveness? Front. Physio. 3:312. doi: 10.3389/fphys.2012.00312
Received: 28 May 2012; Paper pending published: 27 June 2012;
Accepted: 15 July 2012; Published online: 31 July 2012.
Copyright © 2012 Kumar and Foster. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Rakesh K. Kumar, Department of Pathology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. e-mail: email@example.com