COLUMBIA, Mo. – Cystic Fibrosis (CF) continues to be a lethal disease for humans despite the identification of the problematic gene two decades ago. Many humans born with CF – the most common genetic disease in Caucasians - often die because of a lung disease developed later. Scientists have been unable to develop an animal model that develops the fatal lung disease. Now, a University of Missouri researcher is producing pigs born with cystic fibrosis that mimic the exact symptoms of a newborn with CF. The researchers are hopeful that these pigs will continue to mimic the human symptoms so the fatal lung disease can be studied and ultimately treated. The research appears in the journal Science.
"Right now, if you want to do experiments to find treatments or therapies for the lung disease that is fatal for people with CF, you would have to experiment on kids that have CF," said Randy Prather, distinguished professor of reproductive biotechnology in the MU College of Agriculture, Food and Natural Resources. "When the genetic mutation is introduced into mice, they do not display the symptoms of CF. That's why these new swine models are so important. 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."
Prather collaborated with Michael Welsh from the Howard Hughes Medical Institute at the University of Iowa. To create the genetic defect in pigs, a team led by Welsh made genetic modifications in pig cells. Prather's group then generated the genetically modified pigs from the cells using a process known as nuclear transfer. The pigs – called founder animals - that were produced carried only one copy of the mutated gene. Prather bred the pigs naturally and now many piglets have been born with CF.
Once a liter is born, the piglets are immediately flown to Iowa where physicians who perform the corrective surgery on human newborns with CF do the same for the pigs. Meanwhile, MU researchers perform analysis during the transit to determine which piglets have the mutations
"So far, all the mutations in the pigs have exactly mimicked the problems in humans born with CF," Prather said. "The whole cellular physiology of the pig is similar to humans. That's why having this break- through model is so exciting for the potential it has to move research on cystic fibrosis forward."