Cost-effective generation of A-to-G mutant mice by zygote electroporation of adenine base editor ribonucleoproteins

More than 32,000 pathogenic single nucleotide polymorphisms (SNPs) have been identified in the human genome (Gaudelli et al.,2017).Genetically modified mice with pathogenic SNPs are good models for studies of disease pathogenesis and the development of new therapeutics.Accordingly, an efficient, high-throughput method for the generation of mouse models with SNPs is needed.We and others have demonstrated that Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) nuclease-induced homologous recombination (HR), cytidine base editors (CBEs), and adenine base editors (ABEs) are efficient genomeediting tools for generating animal models with pathogenic SNPs (Inui et al., 2014;Liang et al., 2017, Liang et al., 2018;Yang et al., 2018).Base editing by base editors is much more efficient than HR(Komor et al., 2016;Kim et al., 2017;Liang et al., 2017).