As males are unable to produce milk or lay eggs, the ability to breed cows and hens that produce all-female litters is likely to be high on most poultry and dairy farmers’ wish lists.
Now, scientists at the Francis Crick Institute and the University of Kent have come a step closer to realising this goal after successfully using CRISPR gene editing techniques to produce all-female or all-male litters of mice.
The technique could also be used to improve animal welfare in areas of scientific research in which only male or only female animals are required for studies, the researchers say.
To make the breakthrough the researchers took advantage of the fact that CRISPR consists of two parts – the Cas9 enzyme, which cuts the DNA and enables scientists to alter specific regions of genes, and the guide RNA, which carries the Cas9 enzyme to the desired region on the genome.
They targeted the TOP1 gene, which is essential to DNA replication, and placed one part of CRISPR on the father’s X or Y chromosome, meaning that it will only be inherited by female or male embryos, and the other part on the mothers’ chromosomes, which will be inherited by all embryos.
This meant that when a sperm carrying the Cas9 enzyme on the father’s X or Y chromosome fertilised an egg carrying the guide RNA, the gene editing process was triggered in the resulting embryo and it was not able to develop beyond a very early stage.
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“This method works as we split the genome editing process in half, between a male and female, and it is only when the two halves meet in an embryo through breeding, that it is activated. Embryos with both halves cannot develop beyond very early cell stages,” said Charlotte Douglas, first author and former PhD student and postdoctoral scientist at the Crick.
“We’ve also shown this process works successfully in different combinations – introducing either the Cas9 or the guide RNA elements on to the mother’s or father’s chromosomes.”
Using this method, the researchers were able to control the sex of a litter with 100 per cent accuracy and found no harmful effects in the surviving animals.
Moreover, as the TOP1 gene is well conserved across mammals, these results may also be applicable to other animals such as livestock.
“The implications of this work are potentially far-reaching when it comes to improving animal welfare, but should be considered at ethical and regulatory levels,” said Dr Peter Ellis, author and senior lecturer in molecular genetics and reproduction at the University of Kent.
“In particular, before any potential use in agriculture, there would need to be extensive public conversation and debate, as well as changes to legislation. On the scientific side, there is also much work to be done over a number of years. Further research is needed, first to develop the particular gene editing toolkits for different species, and then to check they are safe and effective.”