Precise editing of myostatin signal peptide by CRISPR/Cas9 increases the muscle mass of Liang Guang Small Spotted pigs
Myostatin (MSTN), a member of the transforming growth factor-β superfamily, is a negative regulator of muscle growth and development. Disruption of the MSTN gene in various mammalian species markedly promotes muscle growth. Previous studies have mainly focused on the disruption of the MSTN peptide c...
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Veröffentlicht in: | Transgenic research 2020-02, Vol.29 (1), p.149-163 |
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Sprache: | eng |
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Zusammenfassung: | Myostatin (MSTN), a member of the transforming growth factor-β superfamily, is a negative regulator of muscle growth and development. Disruption of the
MSTN
gene in various mammalian species markedly promotes muscle growth. Previous studies have mainly focused on the disruption of the
MSTN
peptide coding region in pigs but not on the modification of the signal peptide region. In this study, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system was used to successfully introduce two mutations (PVD20H and GP19del) in the
MSTN
signal peptide region of the indigenous Chinese pig breed, Liang Guang Small Spotted pig. Both mutations in signal peptide increased the muscle mass without inhibiting the production of mature MSTN peptide in the cells. Histological analysis revealed that the enhanced muscle mass in MSTN
+/PVD20H
pig was mainly due to an increase in the number of muscle fibers. The expression of MSTN in the
longissimus dorsi
muscle of
MSTN
+/PVD20H
and
MSTN
KO/PVD20H
pigs was significantly downregulated, whereas that of myogenic regulatory factors, including MyoD, Myogenin, and Myf-5, was significantly upregulated when compared to those in the
longissimus dorsi
muscle of wild-type pigs. Meanwhile, the mutations also activated the PI3K/Akt pathway. The results of this study indicated that precise editing of the MSTN signal peptide can enhance porcine muscle development without markedly affecting the expression of mature MSTN peptide, which could exert other beneficial biological functions in the edited pigs. |
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ISSN: | 0962-8819 1573-9368 |
DOI: | 10.1007/s11248-020-00188-w |