Milo Cosmo, a bull calf designed to produce 75% male offspring

Scientists at the University of California, Davis, have successfully produced a calf called Cosmo, which was genome-edited as an embryo to produce more male offspring. The research was presented in a poster today (July 23) at the American Society of Animal Science meeting.

Using the genome-editing technique CRISPR, researchers can make targeted cuts to the genome or insert useful genes, known as gene knock-ins. In this case, scientists successfully inserted or knocked down the cattle SRY gene, the gene responsible for the onset of male development, in a bovine embryo. This is the first demonstration of a targeted gene knock-in for large sequences of DNA via embryo-mediated genome editing in cattle.

“We expect the offspring of Cosmo to develop this inherited lineage and look like males, even if they possess a Y chromosome,” said Alison de Anninam, an animal geneticist at the UC Davisin of Animal Science.

More male, more beef

Van Einnam says that part of the motivation to produce more male cattle is that male cattle are about 15 percent more efficient at converting feed into weight gain. They are more fuel-efficient than women. Additionally, they are processed at a heavy weight.

It can also be a win for the environment, with fewer cattle needing to produce the same amount of beef. “Ranchers can produce some females as replacements and direct a higher proportion of male cattle to market,” said Joey Owen, a postdoctoral researcher in veterinary science who is leading the project with Van Ennenham is.

A difficult journey

The SRY gene was inserted into bovine chromosome 17, which is a genomic safe harbor site. This predictably ensures genetic elements and does not inhibit the expression or regulation of adjacent genes. Chromosome 17 was chosen after unsuccessful attempts to knock out the gene on the X chromosome, resulting in an ox that produced only male offspring. Cosmo is expected to produce 75 percent of male offspring – the normal 50 percent XY animal, and another 25percent XX animal that inherits the SRY gene.

“It took two and a half years to develop a method of inserting a gene into the developing embryo and successfully establishing a pregnancy,” Owen said. But in April of 2020, a healthy 110-pound male calf was born.

“It’s been a real labor of love,” Van Aninum said.

He said that this is the beginning of research. Cosmo will reach sexual maturity in one year, and it will breed to study if inheriting the SRY gene on chromosome 17 is enough to trigger the male developmental pathway in XX embryos, and will result in offspring that grow up. Will go and look like men. As the Food and Drug Administration regulates gene-editing of animals as if they were drugs, Cosmo and their offspring will not enter the food supply.

Other researchers on the team include James Murray, Pablo Ross, Sadie Hennig and Jason Lin with the UC Davis Department of Animal Science, and Brett McNab and Temer Mansour of the UC Davis School of Veterinary Medicine.

The project was supported by the Biotechnology Risk Assessment Grant Program from the US Department of Agriculture, California Agricultural Experiment Station at UC Davis and the USDA NIFA National Needs Graduate and Postgraduate Fellowship.