Researchers have bred mouse pups with genetic material from two male, or two female parents.
Live-born mice have never been successfully bred from two fathers before. This has been achieved previously with bi-maternal pups, but the new paper published last week in Cell Stem Cell details how some of them reached maturity and were able to have their own offspring, which has not been observed before.
'This research shows us what's possible,' said senior author, Dr Wei Li of the Chinese Academy of Sciences in Beijing.
In order to breed the pups, researchers had to overcome a natural process in mammals called imprinting. We receive a full copy of genetic material from each parent, but there are some genes where only the copy from a particular parent will do. This is said to be 'imprinted', while the corresponding material from the other parent is inactivated. When two imprinted sequences are present at the same locus, the embryo will not develop normally.
'The authors have made an extremely important step forward in understanding why mammals can only reproduce sexually,' said Dr Christophe Galichet, from the Francis Crick Institute in London, who was not involved in the research. 'In mammals, some genetic information must be given by mum or dad chromosome in order to generate an offspring.'
Starting with haploid embryonic stem cells (which – like sperm and eggs – contain only one copy of each chromosome) scientists deleted the imprinted material using CRISPR/Cas9. The process was more difficult in cells from male mice because seven regions needed to be removed, compared with three in females.
The team then combined these modified cells with gametes from the second parent mouse, imitating the process of fertilisation. This was complicated for male mice by the fact that their cells then needed to be injected into an donor egg cell with the nucleus removed.
A total of 210 bi-maternal embryos were created, of which 29 (14 percent), resulted in live births and went on to become healthy fertile adults. Of 477 bi-paternal embryos, only 12 live mice were born, which is 3 percent. Of these, only two survived for longer than two days.
'We can't yet make bi-paternal mice that are viable,' Marisa Bartolomei, professor of cell and developmental biology at the University of Pennsylvania Perelman School of Medicine, told STAT News. 'It's because the imprinting is still messed up in these mice.'
Translating this technique to other mammals is unlikely to be straightforward: the set of imprinted genes is unique to each species and needs to be identified for the experiment to work. The possibility of using such technology in humans is still far off: the low number of births as a proportion of embryos created, and the high risk of producing offspring that are abnormal or do not survive is not likely to be acceptable.