| Autor: |
Ming-Ming Chen, Yue Zhao, Xue-Ling Xu, Xiao-Sheng Zhang, Jin-Long Zhang, Su-Jun Wu, Zhi-Mei Liu, Yi-Ming Yuan, Xiao-Fei Guo, Shi-Yu Qi, Guang Yi, Shu-Qi Wang, Huang-Xiang Li, Ao-Wu Wu, Guo-Shi Liu, Kun Yu, Shoulong Deng, Hong-Bing Han, Feng-Hua Lv, Yan Li, Zheng-Xing Lian |
| Rok vydání: |
2023 |
| DOI: |
10.1101/2023.03.09.531872 |
| Popis: |
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 theMSTNoften 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, aMSTNDel273Cmutation withFGF5knockout sheep, in which theMSTNandFGF5dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon ofMSTN, resulting in cysteine-depleted at amino acid position 273, and theFGF5double allele mutation led to inactivation ofFGF5gene. TheMSTNDel273Cmutation withFGF5knockout 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, theMSTNDel273Cmutation withFGF5knockout mediated the activation ofFOSL1via the MEK-ERK-FOSL1 axis. The activatedFOSL1promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the transcription of MyoD1, and resulting in smaller myotubes. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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