文献类型： 外文期刊
作者： Wang, Y. 1 ; Liu, W. J. 1 ; Meng, C. H. 1 ; Wang, H. L. 1 ; Cui, Z. K. 1 ; Zhang, J. 1 ; Zhang, J. L. 1 ; Qian, Y. 1 ; Li, Y. X. 1 ; Cao, S. X. 1 ;
作者机构： 1.Jiangsu Acad Agr Sci, Inst Anim Sci, Nanjing 210014, Peoples R China
2.Jiangsu Prov Engn Res Ctr Precis Anim Breeding, Nanjing 210014, Peoples R China
3.Minist Agr, Key Lab Crop & Anim Integrated Farming, Nanjing 210014, Peoples R China
关键词： Hu sheep; MSTN; CBE; Off-target effects
期刊名称：FUNCTIONAL & INTEGRATIVE GENOMICS （ 影响因子：3.1； 五年影响因子：3.0 ）
ISSN： 1438-793X
年卷期： 2025 年 25 卷 1 期
页码：
收录情况： SCI
摘要： The cytosine base editor (CBE) enables precise C-to-T substitution without inducing DNA double-strand breaks, which offering a promising tool for editing livestock genomes to enhance economically valuable traits. In this study, using Hu sheep, characterized by high reproductive performance but suboptimal meat production as the research subject, two CBE-editing sgRNAs (sgM1 and sgM2) targeting the negative regulator Myostatin (MSTN) gene were designed. The results revealed a 75% editing efficiency of sgM2 at the parthenogenetically activated embryonic level with no detectable off-target effects. Thirty-four zygotes from five Hu sheep microinjected with sgM2 and CBE mRNA mixtures were transferred into four Hu sheep recipient ewes, yielding four lambs with confirmed MSTN editing and no off-target activity. Statistical analysis of growth performance data revealed that MSTN-edited Hu sheep exhibited significantly (P < 0.05) higher body weights at 120-180 days, and significantly (P < 0.05) enlarged muscle fiber cross-sectional areas compared to wild-type controls. Edited Hu sheep displayed reduced MSTN protein expression, elevated p-AKT levels, and diminished p-ERK and p-p38 signaling. In conclusion, MSTN-edited Hu sheep were highly efficient generated using CBE, and further analysis demonstrate that MSTN editing activates the AKT pathway while suppressing MAPK signaling, leading to muscle fiber hypertrophy and accelerated growth, which provides technical methodologies and breeding materials for developing fast-growing, meat-type Hu sheep-germplasm.
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