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

Elife

State Key Laboratory of Animal Biotech Breeding, Beijing Key Laboratory for Animal Genetic Improvement, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.

Published: October 2024

Mutations in the well-known Myostatin () 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 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 mutation with knockout sheep, in which the and dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of , resulting in cysteine-depleted at amino acid position 73, and the double allele mutation led to inactivation of gene. The mutation with 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 mutation with knockout mediated the activation of via the MEK-ERK-FOSL1 axis. The activated 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 Ca-dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452178PMC
http://dx.doi.org/10.7554/eLife.86827DOI Listing

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