New Pig Model of Cystic Fibrosis Lays Groundwork
for Better Understanding of Human Disease
For the first time, researchers have developed a genetically
altered animal model for cystic fibrosis (CF) that closely matches
the characteristics of the disease in humans. By studying the complex
and multi-organ disease process in the pig model, researchers can
now better understand how the complications of CF develop, an advancement
that may lead to new avenues for research in prevention and treatment.
The study, published in the Sept. 26 edition of Science, was funded in part by
the National Heart, Lung, and Blood Institute (NHLBI), along with
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), both of the National Institutes of Health, as well as
the Cystic Fibrosis Foundation.
CF is an inherited disease of the mucus-secreting glands which is caused by mutations
in the gene responsible for making the protein cystic fibrosis
transmembrane conductance regulator (CFTR), important for making
sweat, digestive juices, and mucus. CF affects multiple organs,
including the lungs, pancreas, liver, intestines, sinuses, and
sex organs. In CF, mucus becomes thick and sticky, and builds up
in the lungs and in the pancreas, blocking the airways, and disrupting
the digestive system, resulting in recurrent, destructive infections
and trouble digesting food. Respiratory failure and liver disease
are the most common causes of death in CF.
Before now, mice have been the only animal model for CF. However since mice do
not exhibit typical symptoms of CF, and the lung and liver diseases
found in humans, finding a better model was crucial to furthering
"This represents a significant advance in research on cystic fibrosis. Until now, no animal model has come close to mimicking the disease as seen in humans. This model offers unprecedented opportunities to understand how the respiratory disease develops during childhood which may lead to novel prevention and therapeutic strategies," said Elizabeth G. Nabel, M.D., director, NHLBI.
"This new approach allows researchers to move beyond mouse models into species that are physiologically more similar to humans and that manifest the multi-organ symptoms of the disease. It is an advance for CF research as well as for the study of other diseases where the mouse model is inadequate," said NIDDK Director Griffin P. Rodgers, M.D.
A team of researchers from the University of Iowa and the University of Missouri generated male piglets lacking the CFTR gene, or possessing the most common mutation of the gene, which was identified in 1989. Newborn piglets born without CFTR had similar presentations at birth, and shortly after birth, as seen in human infants with CF, including typical abnormalities in the lungs, intestines, pancreas, and liver.
As is typical in about 15 percent of human infants with CF, newborn piglets without CFTR developed meconium ileus, an intestinal obstruction requiring corrective surgery. All of the piglets developed pancreatic insufficiency. The pigs also exhibited signs of focal biliary cirrhosis, or lesions on the liver, and gallbladder abnormalities, both typical of CF in humans.
Lung disease in CF is caused by infection and inflammation. Which comes first remains an important question for CF researchers. At birth, researchers found no evidence of infection or inflammation in the pigs, a situation similar to newborn humans with CF.
"By tracking how the lungs of these pigs respond to challenges to their respiratory systems introduced by the environment, we hope to better understand how the complications of CF progress in children," said
Michael J. Welsh, M.D., University of Iowa and the Howard Hughes Medical Institute,
and senior author of the study.
About 12 million Americans are carriers of an abnormal CFTR gene. Many of them
do not know that they are CF carriers. About 30,000 people in the United States
have CF. The median life expectancy for a person with CF is 37 years. Currently,
there is no cure for CF, but life expectancy has greatly improved due to better
nutrition and management of respiratory infections.
Additional funding for the research was provided by the Howard Hughes Medical
Institute, Food for the 21st Century.
NIDDK conducts and supports research in diabetes and other endocrine and metabolic
diseases; digestive diseases, nutrition, and obesity; and kidney, urologic, and
hematologic diseases. Spanning the full spectrum of medicine and afflicting people
of all ages and ethnic groups, these diseases encompass some of the most common,
severe, and disabling conditions affecting Americans. For more information about
NIDDK and its programs, see www.niddk.nih.gov.
Part of the National Institutes of Health, the National Heart, Lung, and Blood
Institute plans, conducts, and supports research related to the causes, prevention,
diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and
sleep disorders. The Institute also administers national health education campaigns
on women and heart disease, healthy weight for children, and other topics. NHLBI
press releases and other materials are available online at www.nhlbi.nih.gov.
he National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.