CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes

Charlotte Douglas, Valdone Maciulyte, Jasmin Zohren, Daniel M. Snell, Shantha K. Mahadevaiah, Obah A. Ojarikre, Peter J. I. Ellis () and James M. A. Turner ()
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Charlotte Douglas: Sex Chromosome Biology Laboratory, The Francis Crick Institute
Valdone Maciulyte: Sex Chromosome Biology Laboratory, The Francis Crick Institute
Jasmin Zohren: Sex Chromosome Biology Laboratory, The Francis Crick Institute
Daniel M. Snell: Sex Chromosome Biology Laboratory, The Francis Crick Institute
Shantha K. Mahadevaiah: Sex Chromosome Biology Laboratory, The Francis Crick Institute
Obah A. Ojarikre: Sex Chromosome Biology Laboratory, The Francis Crick Institute
Peter J. I. Ellis: University of Kent
James M. A. Turner: Sex Chromosome Biology Laboratory, The Francis Crick Institute

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Animals are essential genetic tools in scientific research and global resources in agriculture. In both arenas, a single sex is often required in surplus. The ethical and financial burden of producing and culling animals of the undesired sex is considerable. Using the mouse as a model, we develop a synthetic lethal, bicomponent CRISPR-Cas9 strategy that produces male- or female-only litters with one hundred percent efficiency. Strikingly, we observe a degree of litter size compensation relative to control matings, indicating that our system has the potential to increase the yield of the desired sex in comparison to standard breeding designs. The bicomponent system can also be repurposed to generate postnatal sex-specific phenotypes. Our approach, harnessing the technological applications of CRISPR-Cas9, may be applicable to other vertebrate species, and provides strides towards ethical improvements for laboratory research and agriculture.

Date: 2021
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DOI: 10.1038/s41467-021-27227-2

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