Translational Animal Models in Drug Discovery and Development

Author(s): Jason H.T. Bates, Mercedes Rincon and Charles G. Irvin

DOI: 10.2174/978160805469511201010167

Modeling Human Asthma in Animals

Pp: 167-195 (29)

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Abstract

SHS investigation development is considered from the geographical and historical viewpoint. 3 stages are described. Within Stage 1 the work was carried out in the Department of the Institute of Chemical Physics in Chernogolovka where the scientific discovery had been made. At Stage 2 the interest to SHS arose in different cities and towns of the former USSR. Within Stage 3 SHS entered the international scene. Now SHS processes and products are being studied in more than 50 countries.

Abstract

Animal models of asthma play a central role in mechanistic studies into the pathophysiology of asthma. However, asthma is a uniquely human disease that remains poorly understood, and which has so far resisted attempts to reproduce all its complexities faithfully in an animal. Nevertheless, the key asthma phenotypic features of airway hyperresponsiveness and inflammation have been recapitulated in a number of animal species, most commonly through immune sensitization and challenge with a foreign protein in order to produce an allergic inflammatory reaction in the lungs. The mouse has become the most commonly used species to model asthma in this fashion because of its obvious advantages related to cost, gestation period, and the wide range of biological manipulations it can be subjected to. Until recently, the small size of the mouse made assessing its lung physiology a challenge, but modern imaging methodologies coupled with the forced oscillation technique for measuring lung mechanical function now make it possible to phenotype mice in detail. This has significantly advanced our understanding of the immunological, genetic and physiological mechanisms of asthma pathogenesis, particularly as they relate to airways hyperresponsiveness.

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