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Introduction of pathogenic mutations into the mouse Psen1 gene by Base Editor and Target-AID

Author

Listed:
  • Hiroki Sasaguri

    (RIKEN Center for Brain Science
    Tokyo Medical and Dental University)

  • Kenichi Nagata

    (RIKEN Center for Brain Science)

  • Misaki Sekiguchi

    (RIKEN Center for Brain Science)

  • Ryo Fujioka

    (RIKEN Center for Brain Science)

  • Yukio Matsuba

    (RIKEN Center for Brain Science)

  • Shoko Hashimoto

    (RIKEN Center for Brain Science)

  • Kaori Sato

    (RIKEN Center for Brain Science)

  • Deepika Kurup

    (RIKEN Center for Brain Science
    Harvard University)

  • Takanori Yokota

    (Tokyo Medical and Dental University)

  • Takaomi C. Saido

    (RIKEN Center for Brain Science)

Abstract

Base Editor (BE) and Target-AID (activation-induced cytidine deaminase) are engineered genome-editing proteins composed of Cas9 and cytidine deaminases. These base-editing tools convert C:G base pairs to T:A at target sites. Here, we inject either BE or Target-AID mRNA together with identical single-guide RNAs (sgRNAs) into mouse zygotes, and compare the base-editing efficiencies of the two distinct tools in vivo. BE consistently show higher base-editing efficiency (10.0–62.8%) compared to that of Target-AID (3.4–29.8%). However, unexpected base substitutions and insertion/deletion formations are also more frequently observed in BE-injected mice or zygotes. We are able to generate multiple mouse lines harboring point mutations in the mouse presenilin 1 (Psen1) gene by injection of BE or Target-AID. These results demonstrate that BE and Target-AID are highly useful tools to generate mice harboring pathogenic point mutations and to analyze the functional consequences of the mutations in vivo.

Suggested Citation

  • Hiroki Sasaguri & Kenichi Nagata & Misaki Sekiguchi & Ryo Fujioka & Yukio Matsuba & Shoko Hashimoto & Kaori Sato & Deepika Kurup & Takanori Yokota & Takaomi C. Saido, 2018. "Introduction of pathogenic mutations into the mouse Psen1 gene by Base Editor and Target-AID," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05262-w
    DOI: 10.1038/s41467-018-05262-w
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