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

First Author  Sasaguri H Year  2018
Journal  Nat Commun Volume  9
Issue  1 Pages  2892
PubMed ID  30042426 Mgi Jnum  J:266488
Mgi Id  MGI:6209274 Doi  10.1038/s41467-018-05262-w
Citation  Sasaguri H, et al. (2018) Introduction of pathogenic mutations into the mouse Psen1 gene by Base Editor and Target-AID. Nat Commun 9(1):2892
abstractText  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.
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