Although the specific gene responsible for cystic fibrosis (CF), CFTR, has been known for almost 20 years, the failure of CFTR–/– mice to develop human-like CF symptoms has limited the use of this animal model. In order to create an animal model that more closely represents human CF, researchers created transgenic CFTR–/– domestic pigs using tools and methods of mouse genetic manipulation. As with newborn humans, newborn pigs lacking CFTR initially showed no signs of disease. However, within a few days after birth they developed severe symptoms similar to the clinical manifestations of human CF. These symptoms included intestinal blockage (meconium ileus), exocrine pancreatic insufficiency and damage, and liver disease (focal biliary cirrhosis). Respiratory symptoms and lung disease are the primary causes of human CF mortality and morbidity, but symptom onset does not take place immediately; patients begin developing symptoms anywhere between 3 months to several years after birth. Similar to human neonates, the CFTR–/– piglets do not have obvious lung abnormalities at birth, but analyzing CFTR–/– pigs later in life might reveal progressive lung changes over time.