Gender selection
To create litters of same-sex mice, scientists in England and the USA used CRISPR-Cas9
Scientists from the Francis Crick Institute, in collaboration with the University of Kent, used gene editing technology to create mouse litters from only females and only males with 100% efficiency.
The scientists' new method uses a two-element genetic system to inactivate embryos shortly after fertilization, allowing only the desired sex to develop. Such a genetically based method of controlling the sex of offspring can dramatically reduce culling in both industries.
Embryo selection is based on the fact that CRISPR-Cas9 consists of two elements – the Cas9 enzyme, which cuts DNA, allowing scientists to change certain areas, and the guide RNA, which transfers Cas9 to the right place in the genome. The team placed one element of the system on the X- or Y-chromosome of the father, which means that it will be inherited only by female or male embryos, respectively. The other element is introduced by the mother and inherited by all embryos.
They target the Top1 gene, which is necessary for DNA replication and repair. When an embryo was formed from sperm and eggs, each of which contained half of CRISPR-Cas9, gene editing was triggered in it, and it could not develop beyond a very early stage, numbering from 16 to 32 cells.
Using this method, the researchers were able to control the sex of the litter with 100% effect. To get a rodent litter consisting only of males, the researchers edited the X chromosome of the father, that is, only females inherited a harmful mutation, and for a litter of only females, they edited the Y chromosome.
Surprisingly, this method did not lead to a 50% reduction in the number of offspring. Litter sizes ranged from 61% to 72% of the control litters. The researchers suggest that this is due to the fact that animals such as mice produce more eggs than required during each cycle, which allows you to lose some of them at an early stage of development without reducing the size of the litter. This means that in situations where one sex is needed, fewer breeding animals will be needed to produce the same number of offspring of the desired sex.
"This method works when we divide the genome editing process in half, between a man and a woman, and only when the two halves meet in the embryo during reproduction, it is activated. Embryos with both halves cannot develop beyond very early cellular stages," said Charlotte Douglas.
Article by Douglas et al. CRISPR-Cas9 effects facilitate generation of single-sex litters and sex-specific phenotypes published in the journal – VM.
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