Mstn-KO Mouse

Myostatin (MSTN), also known as GDF-8, is a protein belonging to the transforming growth factor-β superfamily. It is a negative regulator of skeletal muscle growth and development, inhibiting the proliferation of myoblasts. Mutations in MSTN can lead to skeletal muscle hyperplasia and hypertrophy, resulting in the "double-muscle" phenotype, which is of great significance for improving livestock meat production and has potential implications in treating muscle-related diseases in humans [1,2].

Mutant MSTN gene in cloned goats led to a "double-muscle" phenotype, with muscle fibers tightly arranged and thick, and higher monthly body weight compared to wild-type goats [1]. In sheep, a MSTNDel73C mutation with FGF5 knockout produced a dominant "double-muscle" phenotype, promoting skeletal muscle myofiber hyperplasia through the MEK-ERK-FOSL1 axis [2]. In Hu sheep, MSTN-edited animals showed a double-muscled phenotype, higher body weight at 3 and 4 months old, and enhanced AKT and suppressed ERK1/2 signaling in the gluteus muscle [3].

In conclusion, MSTN is a crucial negative regulator of skeletal muscle growth. Gene-edited animal models with MSTN mutations, such as goats, sheep, and pigs, have demonstrated its role in enhancing muscle mass and growth. These findings have implications for livestock breeding to improve meat production and potentially for developing treatments for muscle-loss-related human diseases [1,2,3].

References:

1. Song, Shao-Zheng, He, Zheng-Yi, Cheng, Yong, Zhang, Ting, Li, Dan. . MSTN modification in goat mediated by TALENs and performance analysis. In Yi chuan = Hereditas, 44, 531-542. doi:10.16288/j.yczz.22-011. https://pubmed.ncbi.nlm.nih.gov/35729101/

2. Chen, Ming-Ming, Zhao, Yue, Yu, Kun, Lian, Di, Lian, Zheng-Xing. 2024. A MSTNDel73C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia. In eLife, 12, . doi:10.7554/eLife.86827. https://pubmed.ncbi.nlm.nih.gov/39365728/

3. Guo, Rihong, Wang, Huili, Meng, Chunhua, Zhong, Jifeng, Cao, Shaoxian. 2023. Efficient and Specific Generation of MSTN-Edited Hu Sheep Using C-CRISPR. In Genes, 14, . doi:10.3390/genes14061216. https://pubmed.ncbi.nlm.nih.gov/37372396/