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Precise generic mutation of model animals is highly valuable for functional investigation of human mutations.Clustered regularly interspaced short palin-dromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-induced homology.directed repair (HDR) is usually used for precise genetic mutation,being limited by the relatively low efficiency compared with that of non-homologous end joining (NHEJ).Although inhibition of NHEJ was shown to enhance HDR-derived mutation,in this work,without inhibition of NHEJ,we first generated gene-modified pigs harboring precise orthologous human mutation (Sox10 c.A325≥T) via CRISPR/Cas9-induced HDR in zygotes using single.strand oligo DNA (ssODN) as template with an efficiency as high as 80%,indicating that pig zygotes ex-hibited high activities of HDR relative to NHEJ and were highly amendable to genetic mutation via CIRSPR/Cas9.induced HDR.Besides,we found a higher concentra-tion of ssODN remarkably reduced HDR-derived mu-tation in pig zygotes,suggesting a possible balance for optimal HDR-derived mutation in zygotes between the excessive accessibility to HDR templates and the activi.ties of HDR relative to NHEJ which appeared to be neg-atively correlated to ssODN concentration.In addition,the HDR-derived mutation,as well as those from NHEJ,extensively integrated into various tissues including gonad of founder pig without detected off-targeting,suggesting CRISPR/Cas9.induced HDR in zygotes is a reliable ap-proach for precise genetic mutation in pigs.