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 ferrets and pigs that replicate many of the key features of human CF disease including intestinal obstruction, exocrine pancreatic destruction, micro-gallbladder, vas deferens abnormalities, focal biliary cirrhosis, congenital airway structural abnormalities, and airway and sinus infection with time. The goals of the Animal Models Core will be to (1): Provide Program investigators with non-CF and CF ferrets and pigs, and to build new genetically engineered CF ferret and pig models that express CFTR in a regulated fashion; (2) Assist projects in carrying out vector delivery, the harvesting of biologic samples from live animals (e.g., bronchoalveolar lavage fluid and blood), and the care and analysis of study animals; (3) Facilitate studies by monitoring disease progression with high resolution computed tomography sinus and lung imaging, and measuring mucociliary transport. The Animal Models Core will function seamlessly through already established interactions with the Project Leaders, Pathology Core, In Vitro Models and Cell Culture Core, Vector Core, and the Administrative Core. The success of the Animal Models Core is ensured because of the commitment, experience, and expertise that the personnel bring to the Core.
CORE A ? ANIMAL MODELS PROJECT NARRATIVE Cystic fibrosis is a common life-shortening genetic disease that causes progressive lung failure due to recurrent infections and chronic inflammation. These studies will use cystic fibrosis ferrets and pigs to develop better therapies for cystic fibrosis lung disease.
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