Animal Models of Asthma
Models are devised to allow the study of the components of the physiological system involved in a disease process. The ability to study the response of the system to perturbations, such as inciting stimuli or response modifying agents, for example drugs or neutralizing antibodies, permits conclusions to be drawn concerning cause and effect relationships in the putative cascade of events in the disease. A satisfactory model of human disease is one that not only reproduces one or more of the key elements of the disease but is reproducible and readily accessible to investigators. Models have been developed classically by driving physiological systems with various stimuli that may or may not be encountered in a physiological context, such as allergen or gaseous pollutants, or at least not in the concentrations used to elicit responses in the animal. One of the lessons that the successful development of such a model teaches is that exuberant responses of otherwise normal physiological systems are often at the root of diseases such as asthma. Furthermore, the characteristic that distinguishes the affected animal or human subject may not be clearly outside the range spanned by a normal population. The concordance of several alterations in function may be required to place the host on the susceptible end of a scale describing the risk of disease. Diseases of the above type are generally the result of the interaction of environmental factors and several risk-related genes. In some cases single gene alterations may have sufficiently profound consequences for function that disease results. In such cases modeling of the disease in animals requires another approach. One such approach is the design of a defective gene in an animal. The advent of transgenic and knock-out technologies has allowed investigators to delete or over-express gene products of interest while examining the consequences of these interventions on physiological functions. This intervention is confined to murine models to date. This paper will not address models based on genetic approaches.
KeywordsAirway Inflammation Airway Smooth Muscle Respir Crit Allergen Challenge Airway Hyperresponsiveness
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