In a breakthrough that promises to revolutionize the precision breeding of animals, an international team of scientists led by Jon Oatley, a reproductive biologist with Washington State University's College of Veterinary Medicine, has for the first time used the CRISPR gene editing tool to produce infertile animals that become "surrogate sires" and produce sperm containing only donor animal DNA
Animal sperm may seem like just the topic to kill dinner party conversation stone dead, but in agricultural circles it's big business, with a sample from a prize cattle bull bring around US$50,000 on the market, while a prize race horse's can go as high as US$75,000.
Aside from the monetary value, top tier sires of horses, pigs, cattle, and goats have a real potential for improving livestock to increase food yields while reducing their ecological impact. The problem is that spreading this preferred genetic inheritance is difficult and expensive, especially in poor, remote regions that need it most.
One way to get around this bottleneck is by selective breeding and artificial insemination, but this still often requires the male and the female to be close by or have their movements restricted. The latter is easy for dairy cattle, which spend a lot of time close to the sheds, but it's hard with beef cattle, which must be free to roam and graze. It's even worse for pigs, whose sperm does't survive freezing well, or goats, who don't take well to artificial insemination under the best of conditions.
Otley's team's new approach, which they've been developing for six years, is to essentially turn a not-so-prize sire into a prize one by altering it genetically. Using the CRISPR-Cas9 gene-editing tool they produced mice, pigs, goats, and cattle that lack the gene NANOS2, which controls male fertility, but not female.
The result is a sterile male that produces no sperm. The team then transplanted sperm-producing stem cells from a donor animal into the sterile animal's testes. The recipient animal then produced sperm containing only the donor's genetic information.
So far, the concept has been proven in mice after healthy offspring carrying the genes of donor mice were fathered by surrogate mice, though the larger animals have not been bred yet. However, if it does work, it would mean that prize genetic characteristics could be widely disseminated by simple, natural reproduction. In addition, knocking out the NANOS2 gene doesn't affect female fertility, so sterile males to be serve as surrogate sires could also be bred as needed.
The result of this could be animals that not only produce more and better food but are also more disease-resistant and heat-tolerant. It could also be a tool for rescuing endangered species from extinction or for combating the effects of inbreeding.
However, the team says the biggest hurdle now isn't technical, but political. This is because present regulations won't allow such gene-edited surrogate sires into the food chain, so policies outside the lab would need to be addressed.
"With this technology, we can get better dissemination of desirable traits and improve the efficiency of food production," says Oatley. "This can have a major impact on addressing food insecurity around the world. If we can tackle this genetically, then that means less water, less feed, and fewer antibiotics we have to put into the animals."
The research was published in the Proceedings of the National Academy of Sciences.
Source: Washington State University
