Scientists have created a flock of sheep that carries the gene for a deadly brain disease in humans. The disease, the Batten disease, usually begins in childhood and is inevitably fatal, often within a few years of diagnosis.
The project to test the treatment of the disease is based on cloning techniques at the University of Edinburgh's Roslin Institute. Scientists recognize that the approach may be controversial because it involves the creation of animals that are programmed to die emphasize, however, that their goal is to alleviate human suffering.
"We have the intentionally recreated state in a large mammal because sheep have a brain of similar size and complexity as a child," said Tom Wishart, project manager. "This means that treatments we test on them are more likely to be relevant to humans than those tested on cell cultures or mice and rats."
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There are several types of Batten disease, he added. "One of the faster guys is CLN1, and that's what we've modeled on our sheep."
The Roslin scientists used the gene-editing method Crispr-Cas9 to create the defective CLN1 gene in sheep. "We've collected sheep embryos from the slaughterhouse," said Wishart. "Then we fertilized them and added Crispr reagents to modify their genetic structure before implanting the embryos into the uterus of a replacement sheep." They showed many symptoms of Batten disease, including changes in behavior and brain size. "The progression of the disease in sheep was very similar to that in children," said Wishart. "That was crucial because it showed that we had created an accurate model of Batten's disease."
Other sheep were engineered to carry only a single copy of the gene. "These are asymptomatic carriers, like the parents of children with Batten disease," said Wishart. "From these we can breed sheep that have two faulty copies of the CLN1 gene. These will develop a disease like these children and test our therapies.
Researchers are working on several treatments, including gene therapy, in which healthy genes are transmitted by viruses to replace mutated versions. Many of these techniques are being developed using cell culture and research in mice and rats.
"These studies are crucial to fundamental discoveries," said Wishart. "But if we do not use these few larger animals to refine these discoveries, all of this early work could be wasted.
" It's a dreadful need – to reproduce such a condition. However, we are talking about using only about 10 animals for this research to ultimately find treatments that could extend the lives of young patients by years.
"Unlike humans, we can examine sheep before their external symptoms develop to gain new understanding of the disease process. This knowledge will be invaluable. "