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Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference in Skeletal Muscle Growth between Transgenic Male and Female Mice.

Ma D, Gao P, Qian L, Wang Q, Cai C, Jiang S, Xiao G, Cui W - Int J Mol Sci (2015)

Bottom Line: Piedmontese cattle breeds have a missense mutation, which results in a cysteine to tyrosine substitution in the mature myostatin protein (C313Y).This loss-of-function mutation in myostatin results in a double-muscled phenotype in cattle.These results provide useful insight and basic theory to future studies on improving pork quality by genetically manipulating myostatin expression or by regulating myostatin activity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. madezun@126.com.

ABSTRACT
Myostatin, a transforming growth factor-β family member, is a negative regulator of skeletal muscle development and growth. Piedmontese cattle breeds have a missense mutation, which results in a cysteine to tyrosine substitution in the mature myostatin protein (C313Y). This loss-of-function mutation in myostatin results in a double-muscled phenotype in cattle. Myostatin propeptide is an inhibitor of myostatin activity and is considered a potential agent to stimulate muscle growth in livestock. In this study, we generated transgenic mice overexpressing porcine myostatin missense mutant (pmMS), C313Y, and wild-type porcine myostatin propeptide (ppMS), respectively, to examine their effects on muscle growth in mice. Enhanced muscle growth was observed in both pmMS and ppMS transgenic female mice and also in ppMS transgenic male mice. However, there was no enhanced muscle growth observed in pmMS transgenic male mice. To explore why there is such a big difference in muscle growth between pmMS and ppMS transgenic male mice, the expression level of androgen receptor (AR) mutant AR45 was measured by Western blot. Results indicated that AR45 expression significantly increased in pmMS transgenic male mice while it decreased dramatically in ppMS transgenic male mice. Our data demonstrate that both pmMS and ppMS act as myostatin inhibitors in the regulation of muscle growth, but the effect of pmMS in male mice is reversed by an increased AR45 expression. These results provide useful insight and basic theory to future studies on improving pork quality by genetically manipulating myostatin expression or by regulating myostatin activity.

No MeSH data available.


Related in: MedlinePlus

Increased body mass and skeletal muscle weight of pmMS transgenic female mice compared with wild-type mice. (A,B): Increased body mass in pmMS transgenic female mice, pictures taken from different angles; (C–E): Increased muscling in pmMS transgenic female mice. WT, wild type.
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ijms-16-20020-f002: Increased body mass and skeletal muscle weight of pmMS transgenic female mice compared with wild-type mice. (A,B): Increased body mass in pmMS transgenic female mice, pictures taken from different angles; (C–E): Increased muscling in pmMS transgenic female mice. WT, wild type.

Mentions: To determine whether the expression of pmMS or ppMS in transgenic mice has any effect on muscle growth, we dissected the skeletal muscle of the hind limb that contains the gastrocnemius, rectusfemoris, tibialis anterior (TA), and pectoralis, and measured each muscle’s weight, respectively. The average body weight increased by 6.54% and 9.48% in pmMS and ppMS transgenic female mice, respectively, compared to WT mice (Table 1). The average weight of each individual muscle increased by 17.46%, 32.36%, 35.75%, and 22.16% in pmMS transgenic female mice, and 32.06%, 58.84%, 38.41%, and 41.79% in ppMS transgenic female mice, respectively, compared to WT mice (Table 1). However, the muscle mass weight did not change in pmMS transgenic male mice, while it increased by 31.74%, 52.71%, 49.64%, and 37.61% in ppMS transgenic male mice compared with WT mice (Table 1). Figure 2A,B show pictures of a representative WT female mouse and a representative pmMS female mouse. Figure 2C–E show the hind limb and pectoralis from a pmMS transgenic female mouse and a WT female mouse, respectively. It is clear that the transgenic pmMS female mouse looks more muscular than the WT mouse. The weight of viscus did not change in both types of transgenic mice compared with WT mice (data not shown).


Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference in Skeletal Muscle Growth between Transgenic Male and Female Mice.

Ma D, Gao P, Qian L, Wang Q, Cai C, Jiang S, Xiao G, Cui W - Int J Mol Sci (2015)

Increased body mass and skeletal muscle weight of pmMS transgenic female mice compared with wild-type mice. (A,B): Increased body mass in pmMS transgenic female mice, pictures taken from different angles; (C–E): Increased muscling in pmMS transgenic female mice. WT, wild type.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4581338&req=5

ijms-16-20020-f002: Increased body mass and skeletal muscle weight of pmMS transgenic female mice compared with wild-type mice. (A,B): Increased body mass in pmMS transgenic female mice, pictures taken from different angles; (C–E): Increased muscling in pmMS transgenic female mice. WT, wild type.
Mentions: To determine whether the expression of pmMS or ppMS in transgenic mice has any effect on muscle growth, we dissected the skeletal muscle of the hind limb that contains the gastrocnemius, rectusfemoris, tibialis anterior (TA), and pectoralis, and measured each muscle’s weight, respectively. The average body weight increased by 6.54% and 9.48% in pmMS and ppMS transgenic female mice, respectively, compared to WT mice (Table 1). The average weight of each individual muscle increased by 17.46%, 32.36%, 35.75%, and 22.16% in pmMS transgenic female mice, and 32.06%, 58.84%, 38.41%, and 41.79% in ppMS transgenic female mice, respectively, compared to WT mice (Table 1). However, the muscle mass weight did not change in pmMS transgenic male mice, while it increased by 31.74%, 52.71%, 49.64%, and 37.61% in ppMS transgenic male mice compared with WT mice (Table 1). Figure 2A,B show pictures of a representative WT female mouse and a representative pmMS female mouse. Figure 2C–E show the hind limb and pectoralis from a pmMS transgenic female mouse and a WT female mouse, respectively. It is clear that the transgenic pmMS female mouse looks more muscular than the WT mouse. The weight of viscus did not change in both types of transgenic mice compared with WT mice (data not shown).

Bottom Line: Piedmontese cattle breeds have a missense mutation, which results in a cysteine to tyrosine substitution in the mature myostatin protein (C313Y).This loss-of-function mutation in myostatin results in a double-muscled phenotype in cattle.These results provide useful insight and basic theory to future studies on improving pork quality by genetically manipulating myostatin expression or by regulating myostatin activity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. madezun@126.com.

ABSTRACT
Myostatin, a transforming growth factor-β family member, is a negative regulator of skeletal muscle development and growth. Piedmontese cattle breeds have a missense mutation, which results in a cysteine to tyrosine substitution in the mature myostatin protein (C313Y). This loss-of-function mutation in myostatin results in a double-muscled phenotype in cattle. Myostatin propeptide is an inhibitor of myostatin activity and is considered a potential agent to stimulate muscle growth in livestock. In this study, we generated transgenic mice overexpressing porcine myostatin missense mutant (pmMS), C313Y, and wild-type porcine myostatin propeptide (ppMS), respectively, to examine their effects on muscle growth in mice. Enhanced muscle growth was observed in both pmMS and ppMS transgenic female mice and also in ppMS transgenic male mice. However, there was no enhanced muscle growth observed in pmMS transgenic male mice. To explore why there is such a big difference in muscle growth between pmMS and ppMS transgenic male mice, the expression level of androgen receptor (AR) mutant AR45 was measured by Western blot. Results indicated that AR45 expression significantly increased in pmMS transgenic male mice while it decreased dramatically in ppMS transgenic male mice. Our data demonstrate that both pmMS and ppMS act as myostatin inhibitors in the regulation of muscle growth, but the effect of pmMS in male mice is reversed by an increased AR45 expression. These results provide useful insight and basic theory to future studies on improving pork quality by genetically manipulating myostatin expression or by regulating myostatin activity.

No MeSH data available.


Related in: MedlinePlus