Groundbreaking use of CRISPR selects intercourse of mice with 100% effectivity

Researchers at Francis Crick Institute and the College of Kent have used the CRISPR gene-editing system to supply litters of mice which can be one hundred pc both male or feminine. The approach may assist forestall the pointless culling of animals of undesirable intercourse in agriculture or scientific experiments.

Solely feminine chickens lay eggs, and solely feminine cows produce milk, that means the males of each species are often culled quickly after beginning. For some experiments, scientists may also require both male or feminine animals to check sex-specific ailments reminiscent of ovarian or prostate most cancers. At present, there aren’t any methods to reliably produce one intercourse over the opposite in mammals.

So for this new examine, the workforce investigated how you can use CRISPR-Cas9 to regulate which intercourse is born from a litter of mice. The intention was to make sure solely the specified intercourse can develop past an early embryo stage, and the approach can work to pick for both male or feminine as required.

CRISPR-Cas9 is made up of two primary parts – the Cas9 enzyme cuts the cell’s DNA, and a information RNA sequence tells it the place to make that edit. To make CRISPR intercourse selective, the workforce break up these parts up among the many dad or mum mice. The mom contributes the information RNA, whereas Cas9 is positioned on one of many father’s chromosomes, relying on which intercourse is desired for the pups.

As soon as the 2 elements mix within the embryo, they edit a gene known as Top1, which is crucial for DNA replication. With that gene disrupted, the embryo can not develop past 16 to 32 cells. If Cas9 is on the daddy’s X chromosome, solely females will inherit the mutation, leading to an all-male litter. For an all-female litter, Cas9 is positioned on the Y chromosome.

The approach labored extraordinarily effectively. The workforce bred 72 litters – 36 of every variation – and each single pup born was the specified intercourse. The scientists anticipated that every litter could be smaller, since roughly half of the embryos didn’t develop, however to their shock the litter sizes had been between 61 and 72 p.c the dimensions of unedited management litters.

Importantly, the gene edits had no dangerous unwanted effects on the well being of the mouse pups born. They’ll go on to have their very own litters, which might have pure 50/50 intercourse ratios or, if selectively bred with a mouse containing the opposite half of the CRISPR code, have single-sex litters.

The workforce says that the focused Top1 gene is conserved throughout mammals, so the approach may additionally apply to different instances the place it’s helpful to regulate the intercourse of offspring. Additional analysis shall be wanted to check how effectively it really works in different animals, however for now it might be utilized to laboratory mice.

The analysis was revealed within the journal Nature Communications.

Supply: Francis Crick Institute

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