Cystic fibrosis (CF) is a common autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CF affects multiple organs, including lungs, pancreas, intestine, liver, sweat glands, gallbladder and the male genital tract. Airway infection and inflammation currently cause most of the morbidity and mortality. Although several therapies have improved the lives of patients, current treatments are inadequate and CF 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 for CF lung disease. A major impediment to addressing these issues has been limitations of current animal models. Although mouse strains carrying null and missense CFTR mutations have made enormous contributions, CF mice do not develop the airway or pancreatic disease typically found in humans. We recently generated CF pigs that replicate many of the key features of human CF disease including intestinal obstruction, exocrine pancreatic destruction, micro-gallbladder, vas deferens abnormalities, focal billary cirrhosis, congenital airway structural abnormalities, and airway and sinus infection with time. The goals ofthe Animal Core will be to (1) Provide Program investigators with CF and non-CF pigs;(2) Help Program investigators successfully accomplish the aims of their Projects. The Animal Core will function seamlessly through already established interactions with the Project Leaders, Morphology Core, Imaging Core, and the Administrative Core. The success ofthe Animal Models Core is ensured because ofthe commitment, experience, and expertise that the personnel bring to the Core.

Public Health Relevance

Cystic fibrosis is a corhmon life-shortening genetic disease that causes progressive lung failure due to recurrent infections and chronic inflammation. These studies will use the new cystic fibrosis pig model to better understand the early events in cystic fibrosis lung disease, thereby leading to better therapies.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Iowa City
United States
Zip Code
Weldon, Sinéad; McNally, Paul; McAuley, Danny F et al. (2014) miR-31 dysregulation in cystic fibrosis airways contributes to increased pulmonary cathepsin S production. Am J Respir Crit Care Med 190:165-74
Derscheid, Rachel J; van Geelen, Albert; Berkebile, Abigail R et al. (2014) Increased concentration of iodide in airway secretions is associated with reduced respiratory syncytial virus disease severity. Am J Respir Cell Mol Biol 50:389-97
Hoegger, Mark J; Awadalla, Maged; Namati, Eman et al. (2014) Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs. Proc Natl Acad Sci U S A 111:2355-60
Berkebile, Abigail R; McCray Jr, Paul B (2014) Effects of airway surface liquid pH on host defense in cystic fibrosis. Int J Biochem Cell Biol 52:124-9
Awadalla, Maged; Miyawaki, Shinjiro; Abou Alaiwa, Mahmoud H et al. (2014) Early airway structural changes in cystic fibrosis pigs as a determinant of particle distribution and deposition. Ann Biomed Eng 42:915-27
Reznikov, Leah R; Abou Alaiwa, Mahmoud H; Dohrn, Cassie L et al. (2014) Antibacterial properties of the CFTR potentiator ivacaftor. J Cyst Fibros 13:515-9
Hoegger, Mark J; Fischer, Anthony J; McMenimen, James D et al. (2014) Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. Science 345:818-22
Sun, Xingshen; Olivier, Alicia K; Liang, Bo et al. (2014) Lung phenotype of juvenile and adult cystic fibrosis transmembrane conductance regulator-knockout ferrets. Am J Respir Cell Mol Biol 50:502-12
Gibson-Corley, K N; Olivier, A K; Meyerholz, D K (2013) Principles for Valid Histopathologic Scoring in Research. Vet Pathol :
Ramachandran, Shyam; Karp, Philip H; Osterhaus, Samantha R et al. (2013) Post-transcriptional regulation of cystic fibrosis transmembrane conductance regulator expression and function by microRNAs. Am J Respir Cell Mol Biol 49:544-51

Showing the most recent 10 out of 38 publications