Genome-edited bull can produce more males

American researchers inserted a gene that is involved in male sexual development into one of the calf’s chromosomes

Scientists at the University of California, Davis, have successfully produced a bull calf that has been genome-edited to produce more male offspring. They did this by inserting the SRY gene into the bovine chromosome 17.

But what does that mean?

On March 30, a black 50 kilogram calf was born at the UC Davis barn. The pregnancy cost about US$500,000 and a team of scientists was anxious to see if the calf would show how to put more steers on the market.

The calf, named Cosmo, has 60 chromosomes, as do all domestic cattle, which includes 58 autosomes (any of the numbered chromosomes) and two sex chromosomes known as X and Y. Males have one X chromosome and one Y chromosome (XY) while females have two X chromosomes (XX).

The SRY gene gives instructions for making a protein called the sex-determining region Y (SRY) protein and it is involved in male sexual development.

“SRY is an acronym for the sex determining region on the Y chromosome,” said Alison Van Eenennaam, a co-operative extension specialist with the university’s animal science department.

“SRY is actually a gene that is expressed at about day 30 of bovine embryonic development and it triggers the male developmental pathway. It turns on everything about being a boy and suppresses everything about being a girl.”

Van Eenennaam said that the research motivation to produce more male cattle is that males are about 15 percent more efficient at weight gain than females and they tend to be processed at a heavier weight.

Theoretically, ranchers could produce the same amount of meat as their traditional herd but with fewer animals and they would still be able to produce some females as replacements while directing a higher proportion of cattle to market.

Making the research work required the use of CRISPR-Cas9 technology, which is faster, more accurate and more efficient than previous gene-editing methods.

UC Davis researchers took two and a half years to find a successful way to insert a gene into a developing embryo and another two years to successfully establish a pregnancy after a series of failures transferring gene-edited embryos into surrogate heifers. The original plan was to insert (or knock in) the SRY gene on the X chromosome. But that would have produced only male offspring. The goal was to have more males, but not exclusively all males.

“It was a long process and we were never able to do that successfully in the X chromosome,” said Van Eenennaam. “We tried for nearly five years and we were unsuccessful. We ended up moving to chromosome 17, which is known as a genomic safe harbour site. It is a place where you can put a gene and it doesn’t cause any issues or disrupt the expression of adjacent genes.”

Twenty-two genome-edited embryos reached the blastocyst stage, a time when the ball of dividing cells implant into the wall of the uterus. Nine of those indicated a successful knock-in and, at day 7, they were transferred to surrogate heifers. But just one of those, a heifer with ear tag 3113, was confirmed pregnant at day 35 and the fetus confirmed as a male at day 68.

Van Eenennaam said that Cosmo, as an XY male, should be fertile and half his sperm will carry the SRY gene on chromosome 17.

“The interesting question is whether his XX offspring that inherit the SRY gene are going to appear to be male,” she said.

Cosmo is expected to reach sexual maturity next year and the plan is breed him so researchers can study if inheriting the SRY gene on chromosome 17 will actually trigger the male development pathway in XX female embryos and start the process for them to grow and look like males.

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