US scientists have created pigs with cystic fibrosis (CF), a breakthrough that should open the door to a raft of research into the fatal condition.
Initial reports from the study, published in the journal Science, suggest that the pig model is manifesting a number of the early markers for the disease: an abnormal pancreas, liver and gall bladder and meconium ileus (an inability to pass faeces in a newborn) - the first animal model to do so, although no abnormal lung function has yet been detected.
CF affects 8000 people in the UK, and is caused by the inheritance of a mutated version of a gene called CFTR (cystic fibrosis transmembrane regulator) that codes for chloride ion channels important in the production of mucus, sweat and digestive juices. Both copies of the CFTR gene must be mutated for the disease to be present. Prolonged inappropriate production of these vital secretions leads to poor growth, recurrent lung inflammation and infection, progressive disability and multi-system failure.
Two decades have passed since the discovery of CFTR as the root cause of CF, yet still little is known of the pathophysiology of the disorder and few treatments have emerged. Research has stalled due to a lack of good animal models to study disease progression or the efficacy of new drugs.
'Right now, if you want to do experiments to find treatments or therapies for the lung disease that is fatal for people with cystic fibrosis, you would have to experiment on kids that have cystic fibrosis', said Randy Prather, Professor of Reproductive Biology at the University of Missouri, who led the study.
His team of researchers, from the University of Missouri and University of Iowa, used gene targeting to introduce a mutated form of the CFTR into pig cells. The altered cells were then cloned to produce pigs with one normal version and one mutated version of the CFTR gene - making them carriers. These pigs were then bred to produce offspring with two mutated copies of the gene who have gone on to develop the same early symptoms as humans.
'When the genetic mutation is introduced into mice, they do not display the symptoms of cystic fibrosis. That's why these new swine models are so important', Prather explained. He added: 'We have been able to get them through the initial stages of the disease, which they display just like humans, and now we are just waiting for them to grow and potentially develop the lung disease so we can start experimenting in ways that have never been possible'.