For many livestock animals, being born male means an instant death sentence. Male dairy calves are unwanted because they do not produce milk, while male chickens are routinely killed as soon as they hatch because they do not lay eggs.
Now researchers are proposing a radical solution to this slaughter: genetically engineering the animals we eat so that they mostly produce female offspring. The idea could reduce animal suffering and improve farms鈥� profitability, but is likely to collide with public opposition to genetically-modified organisms.
Researchers led by Motti Gerlic and Udi Qimron of Tel Aviv University in Israel have devised a system to ensure that male animals are rarely born. They worked with mice, which are not livestock animals, so their study is a proof of principle rather than something that could immediately be used on farms.
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Bye bye Y
Like humans, female mice have two X chromosomes while males have one X and one Y. The researchers used CRISPR gene editing to automatically destroy Y-chromosomes in unborn embryos, causing them to abort at an early stage.
The team modified the genome of one group of mice to include a key CRISPR enzyme called Cas9, which cuts DNA in specified places.
In a second group of mice, they added markers to three genes on the Y chromosome, making them a target for Cas9. Each gene is essential for embryos to develop, so damaging even one of them would cause the embryo to abort. They targeted three to be extra sure.
In theory, when these two lines of modified mice mated with each other, only female offspring should have been born. The team found that such crosses produced just three males for every 20 females, so the method shows promise, but may need to target more genes to be fully effective.
This compared to a ratio of 23 males to 14 females in a control experiment, in which males carrying the guide RNAs were mated with unmodified females lacking the Cas9 enzyme 鈥� this would allow for the production of male breeders to ensure the animals don鈥檛 die out.
The method is essentially a 鈥済ene drive鈥� 鈥� a way to force a particular mutation to spread through a population 鈥� says Andrea Crisanti of Imperial College London in the UK. In 2018, Crisanti鈥檚 team developed a gene drive that could wipe out populations of malaria-carrying mosquitoes, by spreading a piece of DNA that causes females to develop as males, preventing reproduction. 鈥淭his is an important step, a proof of principle that the technology can work for mammals as well,鈥� he says.
However, opinions are divided on how applicable the method will be for livestock. One issue is that not all animals use XY sex chromosomes. Chickens, like all birds, do it the other way around: males are ZZ and females are ZW. That means the team鈥檚 exact method would not work. However, Crisanti says that could be engineered around. 鈥淚 don鈥檛 think that鈥檚 a big issue.鈥�
It may also not suit the economic realities of rearing cows, says Stephen Butler of the Irish Agriculture and Food Development Authority. The method requires repeatedly inseminating cows and aborting the resulting fetuses until a female calf is conceived, which would be very inefficient, he says. Butler suspects it would be better to use .
The biggest issue is that the technique is unlikely to be approved for use in livestock, because of public opposition to genetic modification and over-strict regulation, says of the University of California, Davis. The Cas9 gene comes from bacteria, making the mice transgenic.聽 If it is transgenic, it will never make it to market, she says.
bioRxiv
