Core B: Animal Models

CORE B – ANIMAL MODELS PROJECT SUMMARY Primary ciliary dyskinesia (PCD) is an autosomal recessive disease caused by mutations in the genes that encode cilia structural proteins. Mutations in the DNAI1 gene are common in people with PCD and characterized by loss of the outer dynein arm (ODA) of the cilia and loss of ciliary beating. Airway infection and inflammation in both upper and lower airways are present in people with PCD and often lead to respiratory failure. Although several therapies have improved the lives of patients, current treatments are inadequate and PCD remains a lethal disease. Our knowledge about the pathogenesis of the disease, its progression, and the state of the neonatal lung is inadequate. These gaps in our knowledge have hindered attempts to develop better treatments and preventions of lung disease. A major impediment to addressing these issues had been limitations of animal models. We generated PCD pigs that replicate the key features of human PCD disease including early sinus abnormalities (mucosal thickening and mucus impaction), early airway abnormalities (air trapping, lobar collapse, thick abnormally elastic mucus), and early infection and inflammation. The goals of the Animal Models Core will be to: (1) Provide Program investigators with WT and PCD pigs so that they can successfully complete their project aims; (2) Assist projects in the harvesting of biologic samples from live animals (e.g., bronchoalveolar lavage fluid and blood), the care and analysis of study animals, record keeping, and coordination of animal usage among projects; (3) Provide scientific support, expertise, and resources for acquisition of image datasets and subsequent analysis; and (4) Help Project Leaders successfully accomplish the aims of their Projects. State-of-the-art image acquisition technology and analysis tools are readily available at the University of Iowa for these Projects. The Animal Models Core will function seamlessly through already established interactions with the Project Leaders and Core Directors. The success of the Animal Models Core is ensured because of the commitment, experience, and expertise that the personnel bring to the Core.