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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

Analysis of myofiber cell size of gastrocnemius from transgenic and WT mice at the age of 30 weeks. (A) Muscle cross-sections from pmMS transgenic female mice; (B) Muscle cross-sections from WT female mice; (C) Muscle cross-sections from pmMS transgenic male mice; (D) Muscle cross-sections from WT male mice; (E) Comparsion of average muscle size between ppMS transgenic mice (male: n = 5; female: n = 5) and WT mice (male: n = 8; female: n = 6) and (F) Comparsion of average muscle size between pmMS transgenic mice (male: n = 5; female: n = 5) and WT mice (male: n = 8; female: n = 6). Scale bars = 50 μm; *p < 0.05,**p < 0.01.
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ijms-16-20020-f003: Analysis of myofiber cell size of gastrocnemius from transgenic and WT mice at the age of 30 weeks. (A) Muscle cross-sections from pmMS transgenic female mice; (B) Muscle cross-sections from WT female mice; (C) Muscle cross-sections from pmMS transgenic male mice; (D) Muscle cross-sections from WT male mice; (E) Comparsion of average muscle size between ppMS transgenic mice (male: n = 5; female: n = 5) and WT mice (male: n = 8; female: n = 6) and (F) Comparsion of average muscle size between pmMS transgenic mice (male: n = 5; female: n = 5) and WT mice (male: n = 8; female: n = 6). Scale bars = 50 μm; *p < 0.05,**p < 0.01.

Mentions: Next, we measured the myofiber size in the gastrocnemius by hematoxylin and eosin and the results show that the mean gastrocnemius fiber size increased by 18.27% and 26.77%, respectively, in pmMS and ppMS transgenic female mice compared with WT mice (Figure 3A,B,E,F). However, compared with WT male mice, the mean gastrocnemius fiber size in pmMS transgenic male mice did not change, but it increased 41.39% in ppMS transgenic male mice (Figure 3C–F).


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)

Analysis of myofiber cell size of gastrocnemius from transgenic and WT mice at the age of 30 weeks. (A) Muscle cross-sections from pmMS transgenic female mice; (B) Muscle cross-sections from WT female mice; (C) Muscle cross-sections from pmMS transgenic male mice; (D) Muscle cross-sections from WT male mice; (E) Comparsion of average muscle size between ppMS transgenic mice (male: n = 5; female: n = 5) and WT mice (male: n = 8; female: n = 6) and (F) Comparsion of average muscle size between pmMS transgenic mice (male: n = 5; female: n = 5) and WT mice (male: n = 8; female: n = 6). Scale bars = 50 μm; *p < 0.05,**p < 0.01.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-20020-f003: Analysis of myofiber cell size of gastrocnemius from transgenic and WT mice at the age of 30 weeks. (A) Muscle cross-sections from pmMS transgenic female mice; (B) Muscle cross-sections from WT female mice; (C) Muscle cross-sections from pmMS transgenic male mice; (D) Muscle cross-sections from WT male mice; (E) Comparsion of average muscle size between ppMS transgenic mice (male: n = 5; female: n = 5) and WT mice (male: n = 8; female: n = 6) and (F) Comparsion of average muscle size between pmMS transgenic mice (male: n = 5; female: n = 5) and WT mice (male: n = 8; female: n = 6). Scale bars = 50 μm; *p < 0.05,**p < 0.01.
Mentions: Next, we measured the myofiber size in the gastrocnemius by hematoxylin and eosin and the results show that the mean gastrocnemius fiber size increased by 18.27% and 26.77%, respectively, in pmMS and ppMS transgenic female mice compared with WT mice (Figure 3A,B,E,F). However, compared with WT male mice, the mean gastrocnemius fiber size in pmMS transgenic male mice did not change, but it increased 41.39% in ppMS transgenic male mice (Figure 3C–F).

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