“It’s exciting,” says Kotaro Sasaki, a developmental biologist at the University of Pennsylvania, who was not involved in the work. Not only have Li and his team been able to avoid a set of imprinting defects, but their approach is the second way scientists have found to create mice using DNA from two males.
The finding builds on research by Katsuhiko Hayashi, now at Osaka University in Japan, and his colleagues. A couple of years ago, that team presented evidence that they had found a way to take cells from the tails of adult male mice and turn them into immature egg cells. These could be fertilized with sperm to create bi-paternal embryos. The mice born from those embryos can reach adulthood and have their own offspring, Hayashi has said.
Li’s team’s more complicated approach was less successful. Only a small fraction of the mice survived, for a start. The team transferred 164 gene-edited embryos, but only seven live pups were born. And those that were born weren’t entirely normal, either. They grew to be bigger than untreated mice, and their organs appeared enlarged. They didn’t live as long as normal mice, and they were infertile.
It would be unethical to do such risky research with human cells and embryos. “Editing 20 imprinted genes in humans would not be acceptable, and producing individuals who could not be healthy or viable is simply not an option,” says Li.
“There are numerous issues,” says Sasaki. For a start, a lot of the technical lab procedures the team used have not been established for human cells. But even if we had those, this approach would be dangerous—knocking out human genes could have untold health consequences.
“There’s lots and lots of hurdles,” he says. “Human applications [are] still quite far.”
Despite that, the work might shed a little more light on the mysterious phenomenon of imprinting. Previous research has shown that mice with two moms appear smaller, and live longer than expected, while the current study shows that mice with two dads are overgrown and die more quickly. Perhaps paternal imprinted genes support growth and maternal ones limit it, and animals need both to reach a healthy size, says Sasaki.
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