Home / Science / Genetically modified cattle “surrogate bulls” successfully created by scientists to transform animal husbandry

Genetically modified cattle “surrogate bulls” successfully created by scientists to transform animal husbandry

Surrogate goat

One of the “surrogate bulls” goats on the WSU Pullman campus. Credit: Washington State University

For the first time, scientists have created pigs, goats and cattle that can act as “surrogate bulls,”

; male sperm-producing animals carrying only the genetic traits of donor animals.

The advance, published on Proceedings of the National Academy of Sciences on September 14, 2020, could accelerate the spread of desirable traits in livestock and improve food production for a growing global population. In addition, it would allow farmers in remote regions better access to the genetic material of elite animals from other parts of the world and allow more precise reproduction of animals such as goats, where artificial insemination is difficult to use.

“With this technology, we can achieve better dissemination of desirable traits and improve the efficiency of food production. This can have a major impact on addressing food insecurity around the world, “said Jon Oatley, reproductive biologist at WSU’s College of Veterinary Medicine.” If we can tackle this problem genetically, it means less water, less feed and less. antibiotics that we have to put in animals “.

A research team led by Oatley used the gene editing tool, CRISPR-Cas9, to eliminate a specific gene for male fertility in animal embryos that would be bred to become surrogate sires. The male animals were then born sterile, but started producing sperm after the researchers transplanted stem cells from donor animals into their testes. The sperm produced by the surrogate bulls contained only the genetic material of the selected donor animals. The genetic modification process employed in this study seeks to make changes within an animal species that could occur naturally, such as infertility.

Jon Oatley

Jon Oatley. Credit: Washington State University

The study is the result of six years of collaborative work between researchers from the WSU, Utah State University, the University of Maryland and the Roslin Institute at the University of Edinburgh in the UK.

The researchers used CRISPR-Cas9 to produce mice, pigs, goats and cattle that lack a gene called NANOS2, specific for male fertility. Male animals grew sterile but otherwise healthy, so when they received sperm-producing stem cells from other animals, they started producing sperm derived from donor cells.

It was confirmed that the surrogate sires had active donor sperm. The surrogate mice generated healthy offspring that carried the genes of the donor mice. The larger animals have not yet been raised. Oatley’s lab is perfecting the stem cell transplant process before taking the next step.

This study provides a powerful demonstration of the concept, said Professor Bruce Whitelaw of the Roslin Institute.

“This shows the world that this technology is real. It can be used, “Whitelaw said.” Now we have to go in and find the best way to use it productively to help feed our growing population. “

Last step in animal husbandry

Scientists have been looking for decades for ways to create surrogate sires to overcome the limitations of selective breeding and artificial insemination, tools that require close proximity to animals or strict control of their movements and, in many cases, both.

Artificial insemination is common in dairy cattle that are often confined, so their reproductive behavior is relatively easy to control, but the procedure is rarely used with beef cattle that need to roam freely to feed. For pigs, the procedure still requires the animals to be close together as pig sperm does not survive freezing well. In goats, artificial insemination is quite challenging and may require a surgical procedure.

Genetics of beef cattle

The technology could be used to improve genetics in beef cattle herds. Credit: Washington State University

Surrogate bull technology could solve these problems as surrogates deliver the donor’s genetic material naturally, through normal reproduction. This allows breeders and herders to let their animals interact normally in the field or in the field. Donors and surrogates do not need to be close to each other as the frozen donor sperm or the surrogate animal itself can be shipped to different places. Furthermore, NANOS2 knockout females remain fertile – as the gene only affects male fertility – and could be bred to efficiently breed infertile males for use as surrogate sires.

This technology has great potential to aid food supply in places in the developing world where shepherds still have to rely on selective breeding to improve their livestock, said Irina Polejaeva, a professor at Utah State University.

“Goats are the number one source of protein in many developing countries,” Polejaeva said. “This technology could enable a faster spread of specific traits in goats, whether it be disease resistance, higher heat tolerance or better meat quality.”

Surrogate sire technology could also open up a new option for the genetic conservation of endangered species, the dwindling numbers of which leave animal communities isolated from each other, limiting their genetic diversity.

Perception and political obstacles

None of the benefits of surrogate bulls can be realized, however, without changing the current landscape of government regulation and public perception.

Even when the technology is advanced enough for commercialization, genetically modified surrogate sires could not be used in the food chain anywhere in the world under current regulations, even if their offspring would not be genetically modified. This is partly due to the misperception that gene editing is the same as controversial gene manipulation, Oatley said. Gene editing involves making changes within a species that could occur naturally. It does not combine DNA from different species.

Oatley realizes that there is a lot of work to be done outside of the laboratory and recently joined the National Task Force on Gene Editing in Livestock to bring together researchers, industry representatives, bioethicists and policy makers to find a path to technology.

“Even if all science was over, the speed at which it can be put into action in livestock production anywhere in the world will be affected by societal acceptance and federal policy,” Oatley said. “By working with policy makers and the public, we can help provide information by assuring the public that this science does not carry the risks that other methods do.”

Reference: “Donor-derived spermatogenesis after stem cell transplantation in a sterile environment NANOS2 male knockout “by Michela Ciccarelli, Mariana I. Giassetti, Deqiang Miao, Melissa J. Oatley, Colton Robbins, Blanca Lopez-Biladeau, Muhammad Salman Waqas, Ahmed Tibary, Bruce Whitelaw, Simon Lillico, Chi-Hun Park, Ki-Eun Park , Bhanu Telugu, Zhiqiang Fan, Ying Liu, Misha Regouski, Irina A. Polejaeva and Jon M. Oatley, September 14, 2020, Proceedings of the National Academy of Sciences.
DOI: 10.1073 / pnas2010102117

This study was supported by the USDA’s National Institute of Food and Agriculture, the WSU Functional Genomics Initiative, and Genus plc. The Roslin Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council, as part of the UK Research and Innovation, and is part of the Royal (Dick) School of Veterinary Studies at the University of Edinburgh. At Utah State University, this study was supported by the Utah Agricultural Experiment Station.

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