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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Charlotte Douglas & Valdone Maciulyte & Jasmin Zohren & Daniel M. Snell & Shantha K. Mahadevaiah & Obah A. Ojarikre & Peter J. I. Ellis & James M. A. Turner, 2021. "CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27227-2
    DOI: 10.1038/s41467-021-27227-2
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    References listed on IDEAS

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    1. Danilo Maddalo & Eusebio Manchado & Carla P. Concepcion & Ciro Bonetti & Joana A. Vidigal & Yoon-Chi Han & Paul Ogrodowski & Alessandra Crippa & Natasha Rekhtman & Elisa de Stanchina & Scott W. Lowe &, 2014. "In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system," Nature, Nature, vol. 516(7531), pages 423-427, December.
    2. Janine A. Clayton & Francis S. Collins, 2014. "Policy: NIH to balance sex in cell and animal studies," Nature, Nature, vol. 509(7500), pages 282-283, May.
    3. Hannah A. Grunwald & Valentino M. Gantz & Gunnar Poplawski & Xiang-Ru S. Xu & Ethan Bier & Kimberly L. Cooper, 2019. "Super-Mendelian inheritance mediated by CRISPR–Cas9 in the female mouse germline," Nature, Nature, vol. 566(7742), pages 105-109, February.
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