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Animal Models for Pulmonary Diseases

Animal models are crucial in advancing our knowledge and understanding of pulmonary diseases. Using alternatives models, such as computer simulations, is simply not advanced enough to elucidate all the biological mechanisms inside a living creature.

Animal modelling in respiratory research must present translational pathologic characteristics to enable researchers to understand complex diseases including pulmonary fibrosis, asthma, and COPD (Chronic Obstructive Pulmonary Disorder). Mice are the primary choice for many research studies, with three main strains of mice typically used in respiratory research, A/J1, BALB/c2, and C57B/63. It is important to note that certain strains are better suited for some applications than others.


Asthma is a respiratory disease with a complex history. Guinea pigs were the most popular models in the past, as they have natural airway hyperresponsiveness and are easily sensitized.4 However, the murine models rapidly became the most commonly used model in the early 1990s.5 Mice are ideal for asthma studies as they are low cost, convenient, and various transgenic models are available. A/J mice have airways that are spontaneously hyperresponsive to bronchoconstricting agents, however BALB/c mice are typically used in immunological studies as they exhibit the TH2-biased immune response and produce monoclonal antibodies to a ovalbumin (OVA) and house dust mite (HDM) allergen.

Pulmonary Fibrosis

Pulmonary fibrosis can be caused by various factors, including diseases, injury, aging, environmental exposures, drug administration, and idiopathic origins. In this application, C57BL/6 mice are the most common strain due to their fully known genome and transgenic possibilities. When developing the model, bleomycin is often used, however the method of bleomycin delivery can alter the pathogenesis. Endotracheal delivery may result in patchy distribution and heterogeneity, while ventilator-assisted drug delivery offers homogeneous distribution with lower doses. 6

Chronic Obstructive Pulmonary Disorder

COPD is an inherently heterogeneous disease, with both emphysema and chronic bronchitis components, controlled by susceptibility factors like environmental exposures and host genetics. The two most common COPD models include elastase delivery and cigarette-smoke exposures. While elastase is useful for simple exposures with rapid and significant lung injury development, it does not replicate the slow progression of COPD development. The gold standard for COPD models is the cigarette-exposure model, as it mimics human exposure more accurately, and A/J mice develop cigarette-smoke-induced emphysema more quickly than other strains.7


  1. https://www.jax.org/strain/000646
  2. https://www.jax.org/strain/000651
  3. https://www.jax.org/strain/000664
  4. Animal models of asthma: Reprise or reboot? (2013). Mullane and Williams Biochemical Pharmacology, 87(1): 131-139
  5. Murine models of allergic asthma. (2017). Hapeslagh et al. Inflammation: Methods and Protocols, Methods in Molecular Biology. Chapter 10. Vol.155
  6. Three-Dimensional Quantitative Co-Mapping of Pulmonary Morphology and Nanoparticle Distribution with Cellular Resolution in Nondissected Murine Lungs.  (2019). Yang L, Feuchtinger A, Möller W, et al. ACS Nano: 13(2):1029-1041
  7. The development of emphysema in cigarette smoke-exposed mice is strain dependent. (2004). Guerassimov A, et al. Am J Respir Crit Care Med 170: 974-980.


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