A MSTNDel73C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia

文献类型： 外文期刊

第一作者： Chen, Ming-Ming

作者： Chen, Ming-Ming;Zhao, Yue;Yu, Kun;Xu, Xue-Ling;Wu, Su-Jun;Liu, Zhi-Mei;Yuan, Yi-Ming;Qi, Shi-Yu;Yi, Guang;Wang, Shu-Qi;Li, Huang-Xiang;Wu, Ao-Wu;Liu, Guo-Shi;Han, Hong-Bing;Lv, Feng-Hua;Lian, Zheng-Xing;Zhang, Xiao-Sheng;Zhang, Jin-Long;Guo, Xiao-Fei;Deng, Shou-Long;Deng, Shou-Long;Lian, Di

作者机构：

关键词： MSTN; FGF5; dual-gene biallelic mutation; FOSL1; myogenesis

期刊名称：ELIFE

ISSN： 2050-084X

年卷期： 2024 年 12 卷

页码：

收录情况： SCI

摘要： Mutations in the well-known Myostatin (MSTN) produce a 'double-muscle' phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional 1:2 to 1:10, which improves the efficiency of the homozygous mutation of biallelic gene. Here, a MSTNDel73C mutation with FGF5 knockout sheep, in which the MSTN and FGF5 dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of MSTN, resulting in cysteine-depleted at amino acid position 73, and the FGF5 double allele mutation led to inactivation of FGF5 gene. The MSTNDel73C mutation with FGF5 knockout sheep highlights a dominant 'double-muscle' phenotype, which can be stably inherited. Both F0 and F1 generation mutants highlight the excellent trait of high-yield meat with a smaller cross-sectional area and higher number of muscle fibers per unit area. Mechanistically, the MSTNDel73C mutation with FGF5 knockout mediated the activation of FOSL1 via the MEK-ERK-FOSL1 axis. The activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the expression of MyoD1, and resulting in smaller myotubes. In addition, activated ERK1/2 may inhibit the secondary fusion of myotubes by Ca2+-dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序