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What have transgenic and knockout animals taught us about respiratory disease?
1The Sackler Institute of Pulmonary Pharmacology, King's College London, London, UK.
Abstract:
Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease.
Insights
Murine models are valuable for studying respiratory diseases like asthma but translating findings to humans remains challenging due to complex disease mechanisms. Improving these models requires a deeper understanding of inflammatory interactions.
Area of Science:
- Respiratory disease research
- Murine models in immunology
- Molecular basis of lung diseases
Background:
- Increasing reliance on murine models for asthma and COPD research over the past decade.
- Potential to investigate complex interactions of cytokines, chemokines, and growth factors in disease.
- Availability of tools like monoclonal antibodies and gene editing for studying signaling pathways.
Purpose of the Study:
- To review the strengths and weaknesses of murine models in respiratory disease research.
- To address the challenges in extrapolating findings from murine models to human conditions.
- To highlight the need for improved modeling of complex inflammatory interactions.
Main Methods:
- Review of existing literature on murine models for respiratory diseases.
- Analysis of the utility of molecular and genetic tools in studying disease pathogenesis.
- Discussion of the limitations in translating preclinical findings to clinical outcomes.
Main Results:
- Murine models offer detailed insights into molecular mechanisms of respiratory diseases.
- Significant challenges exist in direct extrapolation of results to human patients.
- Recent clinical trial disappointments underscore the limitations of current models.
Conclusions:
- Murine models are powerful tools but require refinement for accurate human disease representation.
- Further research is needed to better understand and model the complex inflammatory pathways in respiratory diseases.
- Improved understanding of disease processes is crucial for enhancing the predictive value of animal models.