December 3, 2021

expert reaction to study looking at genome editing to create single sex mice litters

A study published in Nature Communications looks at the use of genome editing technology to generate single-sex litters and sex-specific phenotypes.

Prof Bruce Whitelaw, Prof of Animal Biotechnology, Interim Director of The Roslin Institute, said:

“The work by James Turner, Peter Ellis and colleagues describes a genetic engineering strategy to address an often hidden welfare aspect of agriculture. This team clearly demonstrates what is an elegant molecular genetics approach to produce single-sex litters. They did this in laboratory mice, and technically, it is likely that a similar approach could be deployed in farm species which would have a real welfare impact. This paper highlights how new breeding technologies could be used to address unmet challenges in agriculture. Given the publication of the Nuffield Council’s Report of Genome Editing and Farmed Animal Breeding this week – which emphasises society’s need to balance animal welfare, sustainable food supply, appropriate farming systems, and new technology – whether genetic engineering approaches should be used to generate single-sex litters is both timely and offers a further topic for conversation.”

Prof Malcolm Ferguson-Smith, Emeritus Professor of Pathology, University of Cambridge, said:

“This is a very important contribution from authors I know, and from an outstanding laboratory.

“The press release is clear and concise. The science is robust and the results convincing.

“The work is an advance on previous attempts. It achieves 100% success in producing large litters of same sex mice, and also litters of mice all with the same sex plus the same gene mutation. This can be particularly useful in genetic research as it avoids the sacrifice of mice of unwanted sex/genotype in all current breeding programmes.

“The major implication is for livestock breeding in cattle, pigs and poultry etc., in which the financial outcome depends on the selection of animals of one sex (dairy farming, egg production etc). Current methods (such as sorting X and Y sperm for artificial insemination) are expensive and wasteful. This new approach will take some time to develop in farming; but come it will.

“As with all new developments in biology, there will be ethical concerns about implications for human reproduction. This will doubtless generate much discussion. However, human parents would both require gene editing of germ cells and the requirements for this are formidable and not likely to be contemplated. Sex selection in human offspring (if ever ethical) is possible by less complicated procedures and gene editing is unlikely to be an attractive strategy for this purpose.

“This contribution should be enthusiastically welcomed!”

Dr Harry Leitch, Stem cell biologist and group leader at the MRC London Institute of Medical Sciences, and Academic Clinical Lecturer in Clinical Genetics, Imperial College London, said:

“In this interesting study the authors devise an ingenious strategy to ensure that litters of mice are born either all-male, or all-female. This will be of use for research in mice in which only a single sex is needed – for instance when a particular mutation has an impact only in males or females. This will reduce the number of animals required for any given experiment.

“Furthermore, the authors made the unexpected observation that there is a compensation in litter size – with more animals born in single sex litters, compared to the same sex analysed in mixed litters. The exact mechanism of this compensation is unclear but it makes this strategy even more useful to researchers.

“If applied to livestock species this could reduce the culling of animals and therefore make a significant impact on animal welfare. Although the use of such transgenic technologies in this setting would require extensive publication consultation and a change to existing legislation in the UK.

“As this system requires genetic modification of both parents, it is not applicable to human reproduction.”

‘CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes’ by Charlotte Douglas was published in Nature Communications at 10:00am UK time on Friday 3 December 2021.

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Bruce Whitelaw: “I am a University research scientist working on genome editing technology. My research is funded by public (BBSRC) and commercial sources. I am currently the Interim Director of The Roslin Institute and on the Board of Directors of Roslin Technologies.”

Prof Malcolm Ferguson-Smith: “I have no conflicts of interest.”

Dr Harry Leitch: “No conflicts.”