The Porcine Lung in Biomedical Research

In biomedical research, animal models are frequently necessary for the study of human diseases. Choosing an animal model requires knowledge of several factors that may influence the relevance of the model compared to humans. In particular, anatomy is a relevant feature when choosing animal models. The lungs are essential for survival, but human lungs are not identical to animal lungs and these variations in anatomy can have significance for the study of diseases. In the lungs, large airways are divided into trachea and bronchi that extend into small airways (i.e. bronchioles) and then the respiratory acini (composed of respiratory bronchioles, alveolar ducts and alveoli). The pig lung is similar in overall size and development to humans. In humans, the tracheal cartilage is “C”‐shaped with the open side of the “C” along the posterior border, but in pigs the edges of the cartilage are longer and extend in overlapping fashion along the posterior (or “dorsal”) border. In both species, bronchi begin at the extrapulmonary tracheal bifurcation and extend into the lungs; however, pig bronchi may extend deeper into the lungs (i.e. to approach the pleural border) than humans, thus causing bronchioles of pigs to be less extensive than in humans. Additionally, human bronchi exhibit dichotomous branching (relatively synchronous) whereas pig bronchi exhibit monopodial branching (asynchronous with one main airway and smaller off‐branches). The respiratory acinus has similar organization between species, but humans have a slightly more prominent respiratory bronchiole. How can anatomical differences in lung affect disease? As one example, cystic fibrosis (CF) is a condition caused by mutations in the CF transmembrane conductance regulator ( CFTR ) gene. Shortly after the discovery of the gene in 1989, CFTR ‐deficient mice were generated, but they failed to develop spontaneous CF lung disease. Possible factors for a failure of mice to develop disease included anatomic differences such as lack of intrapulmonary bronchi (i.e. with airway glands and cartilage) and intrapulmonary airways that were equivalent to bronchioles in humans. In 2008, CF pigs were generated and these developed spontaneous CF lung disease like humans. To address the phenotypic differences between these three species, airways were studied and ATP12A, an apical transporter prominent in large but not small airways, was identified as a possible reason for CF disease pigs and human lungs. The presence of ATP12A in bronchi is important for acidification of airways surface liquid in CF and these acidic secretions promote sticky mucus, reduced efficacy of host defenses, and defective mucociliary clearance leading to recurrent/chronic infection and inflammation. In summary, anatomic factors should be considered when developing and trouble‐shooting animal models of human disease. Support or Funding Information NIH and CFF. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .