Fig. 6: Generation of albinism mouse models with high precision using PNLM-pcABE.
From: Protein-nucleic acid language model-assisted design of precise and compact adenine base editor
a Schematic diagram of mouse embryo injection. b The splice acceptor sequence of intron 3 of the mouse Tyr gene was targeted by PNLM-pcABE. The splice acceptor site “AG” is shown in red, and the neighboring adenine is in green. The sgRNA sequence is underlined, and the PAM sequence is in blue. c Genotyping of all F0 generation pups treated with ABE8e (n = 4) and PNLM-pcABE (n = 13). The alleles and frequencies were analyzed by CRISPResso2. The percentage values on the right represent the frequencies of the indicated mutant alleles. The frequency of the wild-type allele was omitted. d, e Phenotypes of F0 mice generated by microinjection of sgRNA and ABEs. In the left photo, the mice were 3 days old, showing the albino phenotype in eye. In the right photo, the mice were 14 days old, exhibiting the albino phenotype in their fur color. f Single A-to-G editing at the indicated Tyr site by ABE8e (n = 4) and PNLM-pcABE (n = 13) in F0 pups. Data are mean ± s.d. (n = 4 independent F0 mice for ABE8e and n = 13 independent F0 mice for PNLM-pcABE), and p values were determined by a two-sided unpaired Wilcoxon rank-sum test (p = 0.0017). g DNA off-target effects at the indicated Tyr site mediated by ABE8e (n = 4) and PNLM-pcABE (n = 13) in F0 pups. Data are mean ± s.d. (n = 4 independent F0 mice for ABE8e and n = 13 independent F0 mice for PNLM-pcABE). Source data are provided as a Source data file.
