title: Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference in Skeletal Muscle Growth between Transgenic Male and Female Mice.
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.
authors: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. madezun@126.com.
authors: Dezun
authors: D
authors: Ma
authors: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. pengfei.gao@yahoo.com.
authors: Pengfei
authors: P
authors: Gao
authors: College of Biological Sciences, China Agricultural University, Beijing 100193, China. lili.qian@yahoo.com.
authors: Lili
authors: L
authors: Qian
authors: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. qingqingwang893@yahoo.com.
authors: Qingqing
authors: Q
authors: Wang
authors: College of Biological Sciences, China Agricultural University, Beijing 100193, China. caichunbobo@126.com.
authors: Chunbo
authors: C
authors: Cai
authors: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. jshengwang@yahoo.com.
authors: Shengwang
authors: S
authors: Jiang
authors: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. gaojunx@yahoo.com.
authors: Gaojun
authors: G
authors: Xiao
authors: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. cuiwentao@caas.cn.
authors: Wentao
authors: W
authors: Cui
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000254:growth & development*; D009154:Mutation; D020125:Mutation, Missense; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D013552:Swine / Q000235:genetics* / Q000378:metabolism
chemical_list: C000607144:AR protein, mouse; D055435:Myostatin; D011944:Receptors, Androgen
keywords: androgen receptor 45; muscle growth; porcine myostatin; transgenic mice