• 생명과학회지
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• 제22권4호
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• pp.486-491
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• 2012

Myostatin (MSTN)은 TGF (transforming growth factor)-beta family에 속하며, 골격근 성장의 억제 조절인자로서 여러 포유류에서 MSTN 유전자 돌연변이는 골격근 증가를 유도한다. MSTN prodomain은 MSTN의 생물학적 활성을 저해하는데, MSTN prodomain이 과 발현된 쥐에서 과도한 근육축적이 확인되었다. 로티퍼(rotifer; Brachionus rotundiformis)는 치어기 어류의 양식산업에 있어 주요한 일차적 먹이생물이다. 그러나 로티퍼에서 MSTN 및 MSTN prodomain의 기능과 발현 유무는 알려져 있지 않다. 따라서 본 연구는 재조합 MSTN prodomains이로티퍼에 미치는 영향에 관하여 조사하고자 하였다. 로티퍼 개체배양 실험을 통하여 재조합 MSTN prodomains(pMALc2x-poMSTNpro, pAMLc2x-sMSTNpro)에 의한 로티퍼의 생식 전 단계, 순 생식단계, 생식 후 단계, 산란, 수명, 포란, 수컷 발생률을 확인하였으며, 또한 pMALc2x-poMSTNpro와 pAMLc2x-sMSTNpro이 밀집배양에서 로티퍼의 개체성장에 영향을 미치는지에 대하여 확인하였다. 그 결과 농도가 1, 2, 4 ${\mu}g/ml$에서 pMALc2x-poMSTNpro를 처리한 실험군과 0.25 ${\mu}g/ml$에서 4 ${\mu}g/ml$ 농도까지 pMALc2x-sMSTNpro를 처리한 실험군에서 로티퍼의 생식 전 단계가 아무처리하지 않은 대조군에 비하여 짧아졌다. 밀집배양 실험에 있어 pMALc2x-poMSTNpro와 pMALc2x-sMSTNpro 모두 로티퍼의 개체 수를 증가를 유도하여, 재조합 MSTN prodomains에 의해서 로티퍼의 reprodution에 영향을 주는 것으로 나타났다. 하지만, 재조합 MSTN prodomains이 어떠한 수용체를 이용하여 신호를 전달하는지에 대한 연구는 앞으로 더 진행되어야 하며, 본 연구의 결과는 재조합 MSTN prodomains이 미세조류에서의 기능 및 메커니즘연구에 중요한 기초자료가 될 것으로 사료된다.

• Fisheries and Aquatic Sciences
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• 제10권1호
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• pp.16-23
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• 2007

Myostatin (GDF8) is a growth factor that limits muscle tissue growth and development in vertebrates. We isolated a myostatin-like gene (Py-MSTN) from the marine invertebrate, the scallop Patinopecten yessoensis. Py-MSTN was highly expressed in the adductor muscle and in the gill unexpectedly. Amino acid analysis showed that Py-MSTN has 49% amino acid sequence identity and 64% similarity to human myostatin (Hs-MSTN), and 42% identity and 61% similarity to myoglianin, the only invertebrate homolog. These results indicated that Py-MSTN may be functionally similar to the vertebrate MSTN than the invertebrate homolog. Phylogenetic analysis suggested that Py-MSTN is an ancestral form of vertebrate MSTN and GDF11 and does not belong to other $TGF-{\beta}$ family members. Molecular modeling showed that Py-MSTN exhibits a similar tertiary structure to mammalian BMP7, a member of $TGF-{\beta}$ family. In addition, the amino acid residues which contact extracellular domain of the receptor were relavively conserved. Given these results, we propose that Py-MSTN is a functionally active member of the $TGF-{\beta}$ family and is involved In muscle growth and regulation.

• Fisheries and Aquatic Sciences
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• 제12권3호
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• pp.185-193
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• 2009

A complete cDNA, which encodes for a myostatin-like protein (Es-MSTN), was isolated from the Chinese mitten crab, Eriocheir sinensis. Es-MSTN was composed of 2,397 nucleotides and the open reading frame (ORF) specified a protein containing 468 amino acids. Es-MSTN exhibited 32% amino acid sequence identity and 52% similarity to human myostatin. Multiple sequence alignment analysis indicated that Es-MSTN possessed the conserved proteolytic cleavage site (RXXR) for maturation of the protein and nine cysteine residues for disulfide bridges. Besides the conserved structural features, Es-MSTN also exhibits its unique characters; a longer N-terminal domain which is involved in protein folding and latent form of myostatin and absence of the cleavage site for BMP-1/tolloid family of metalloproteinase to activate mature myostatin. Phylogenetic analysis suggests that Es-MSTN showed the closely related to both vertebrate myostatin and GDF11. Es-MSTN is expressed highly in the claw muscle, leg muscle, thoracic muscle and heart, and moderately in the hindgut suggesting that Es-MSTN may play important roles in the muscle tissues. As homolog of mammalian myostatin and GDF11, Es-MSTN may be involved in development of muscular tissue and further study will help to produce high-quality seafood.

• Genes and Genomics
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• 제40권11호
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• pp.1119-1125
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• 2018

Melanocortin 4 receptor: (MC4R) and Myostatin (MSTN) are two important growth trait-related genes in animals. In this study, we showed that two SNPs, MC4R-719A>G and MSTN-519C>T, found in the promoters of the MC4R and MSTN genes, respectively, are both associated with growth traits in Spinibarbus hollandi. Furthermore, we observed that there were significant associations between the expression levels of the MC4R and MSTN genes and these two growth trait-related SNPs. The expression level of MC4R gene in brain was lower in GG genotype fish with extremely high growth performance than that in AA genotype fish with extremely low growth performance. Expression level of the MSTN gene in muscle was lower in TT genotype fish with extremely high growth performance than that in CC and CT genotype fish with lower growth performance. The results indicated that these SNPs located in the promoters of MC4R and MSTN are associated with growth-related traits through modification of gene expression levels. The MSTN and MC4R SNPs may have useful application in effective marker-assisted selection aimed to increase output in S. hollandi.

• Journal of Oral Medicine and Pain
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• 제45권4호
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• pp.83-88
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• 2020

Purpose: Growth differentiation factor 11 (GDF11) and myostatin (MSTN) are closely-related transforming growth factor β family members reported to play crucial roles in bone formation. We previously reported that, in contrast to MSTN, GDF11 promotes osteogenesis of vertebrae and limbs. GDF11 has been also reported as an important regulator in tooth development by inducing differentiation of pulp stem cells into odontoblasts for reparative dentin formation. The goal of this study was to investigate the differential roles of GDF11 and MSTN in dental and cranial bone formation. Methods: Micro-computed tomography analysis was performed on cranial bones, including frontal, parietal, and interparietal bones, and lower incisors of wild-type, Gdf11 knockout (Gdf11-/-), and Mstn knockout (Mstn-/-) mice. Tissue volume, thickness, and mineral density were evaluated for both cranial bone and lower incisors. Lower incisor lengths were also measured. Because Gdf11-/- mice die shortly after birth, analysis was performed on newborn (P0) mice. Results: Compared to those of Mstn-/- mice, cranial bone volume, thickness, and mineral density levels were all significantly diminished in Gdf11-/- mice. Tissue mineral density of Gdf11-/- mice were also significantly decreased compared to wild-type mice. Likewise, lower incisor length, tissue volume, thickness, and mineral density levels were all significantly reduced in Gdf11-/- mice compared to Mstn-/- mice. Incisor length was also significantly decreased in Gdf11-/- mice compared to wild-type mice. Mstn-/- mice exhibited mildly increased levels of tissue volume, thickness, and density in cranial bone and lower incisor compared to wild-type mice although statistically not significant. Conclusions: Our findings suggest that GDF11, unlike MSTN, endogenously promotes cranial bone and tooth development.

• Asian-Australasian Journal of Animal Sciences
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• 제20권12호
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• pp.1798-1804
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• 2007

The objective of this study was to assess the association of polymorphisms in MSTN and MYF5 genes with growth traits in three Chinese cattle breeds. Only one homozygous animal with BB genotype at MSTN locus was observed in Jiaxian population which was at Hardy-Weinberg disequilibrium (p<0.05). The frequencies of allele A at MSTN locus and allele B at MYF5 locus in the three Chinese breeds were 0.9550/0.9730/0.9720 and 0.8275/0.7581/0.7523, respectively. Allele A at MSTN locus and allele B at MYF5 locus were dominant in these three populations. No statistically significant differences in growth traits were observed between the genotypes of the Jiaxian breed at MSTN and MYF5 loci and the Nanyang breed at MYF5 locus. However, there were statistically significant differences between the genotypes at MSTN locus of the Nanyang breed for WH, HG, HGI and HGBLR (p<0.05), and of the Qinchuan breed for BLI (p<0.05). The SNP in MYF5 had significant effects on WH and HHC of Qinchuan animals (p<0.05). These results suggest that MSTN and MYF5 are strong candidate genes that influence growth traits in cattle. Other SNPs of MSTN and MYF5 or other linked genes should also be studied, which could lead to the development of selection plans to improve the performance of Chinese cattle and also promote the breeding of genuine beef cattle in China.

• Asian-Australasian Journal of Animal Sciences
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• 제29권10호
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• pp.1500-1507
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• 2016

Myostatin (MSTN) can negatively regulate the growth and development of skeletal muscle, and natural mutations can cause "double-muscling" trait in animals. In order to block the inhibiting effect of MSTN on muscle growth, we transferred zinc-finger nucleases (ZFN) which targeted sheep MSTN gene into cultured fibroblasts. Gene targeted colonies were isolated from transfected fibroblasts by serial dilution culture and screened by sequencing. Two colonies were identified with mono-allele mutation and one colony with bi-allelic deletion. Further, we introduced the MSTN-ZFN mRNA into sheep embryos by microinjection. Thirteen of thirty-seven parthenogenetic embryos were targeted by ZFN, with the efficiency of 35%. Our work established the technical foundation for generation of MSTN gene editing sheep by somatic cloning and microinjection ZFN into embryos.

• Asian-Australasian Journal of Animal Sciences
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• 제26권1호
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• pp.30-35
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• 2013

The myostatin (MSTN) gene, as a negative regulator of skeletal muscle growth, has been proposed to be associated with production traits in farm animals. In the present study, a T/C variant at -125 bp (relative to ATG start codon) of 5'regulatory region of rabbit MSTN was identified by direct sequencing. Two hundred and twenty two rabbits, which were randomly sampled from 3 breeds (Ira rabbits, Champagne rabbits and Tianfu black rabbits), were genotyped by high-resolution melting (HRM). Comparing the genotyping results of 47 samples with direct sequencing, the HRM showed high sensitivity (0.96) and high specificity (0.98). In the three rabbit breeds, the allele C was the predominant allele. The polymorphic site showed high heterozygosity (He = 0.48) and high effective number of alleles (Ne = 1.91). The genetic diversity was reasonably informative (0.25

• 생명과학회지
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• 제31권12호
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• pp.1088-1093
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• 2021

제주마는 한국의 말 품종으로 제주도에서 오랜 기간 자생하여 왔다. 제주마의 기원은 몽골마에서 유래한 것으로 추정되었다. 그러나 최근 연구에서 제주마와 몽골 토종마를 비교 한 결과, 유전적으로 가까우나 제주마가 몽고마와 독립적으로 진화해 온 것으로 보고되었다. 제주마는 경주마로 이용되어 경주 능력이 주요한 경제 형질로 활용되고 있다. Myostatin (MSTN) 유전자는 다양한 포유류에서 골격근량에 영향을 미치는 것으로 연구되었다. Thoroughbred에서 MSTN 유전자 내 존재하는 변이가 경주 능력 및 스태미너에 영향을 미치는 것으로 알려져 있다. 우리는 제주마 1,433두를 포함하여 여러 말 품종의 MSTN 유전자내 변이 빈도를 비교하였다. MSTN 유전자의 g.66493737 변이 중 장거리 적성 유전자형(TT)의 경우 제주마에서 빈도가 0.826으로 한라마(0.285) 및 Thoroughbred (0.252)보다 높은 것으로 확인되었다. 또한 다른 연구를 참고하여 8종 말에서 g.66493737 빈도를 비교하였다. 그 결과, 경주마로 활용되는 품종은 CC형의 빈도가 높았으나, TT형의 빈도는 낮은 것으로 확인되었다. 반대로 승용마 및 역용마 등의 품종은 TT형의 빈도가 높은 것으로 확인되었다. 제주마의 경주 거리(400 m, 800 m, 900 m, 1,000 m, 1,110 m, 1,200 m)별로 유전자형과 도착 기록을 비교 분석했다. 그 결과 1,000 m 이하의 경주에서는 CT형이 TT형보다 더 빠른 도달 기록을 보였다. 그러나 1,110 m 이상의 경주에서는 거의 동일한 결과가 확인되었다. 본 연구에서는 제주마의 MSTN 유전자 변이가 경주 거리 적성과 관련이 있을 수 있음을 시사하였다. 이러한 결과는 추후 연구를 통해 제주마에서 경주 거리 적성 및 경주 능력과 연관된 마커 개발을 위한 자료로 활용이 가능할 것으로 사료된다.

• Fisheries and Aquatic Sciences
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• 제10권2호
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• pp.60-67
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• 2007

Myostatin (MSTN; also known as GDF8) is a member of the transforming growth factor ${\beta}-superfamily$ of proteins. MSTN negatively regulates mammalian skeletal muscle growth and development by inhibiting myoblast proliferation. Mice and cattle possessing mutant MSTN alleles display a 'double muscling' phenotype characterized by extreme skeletal muscle hypertrophy and/or hyperplasia. We isolated the full-length cDNA of a novel MSTN gene from S. schlegeli muscle tissue and examined its expression pattern in various tissues. The full-length gene (GenBank DQ423474) consists of 1941bp with an open reading frame of 1134 bp, encoding 377 amino acids that show 62-92% amino acid similarity to other vertebrate MSTNs. The predicted protein contains a conserved proteolytic cleavage site (RXRR) and nine conserved cysteine residues at the C terminus. RT-PCR revealed that the unprocessed and prodomain myostatin mRNAs were predominantly present in muscle, with limited expression in other tissues. However, the mature myostatin mRNA was highly expressed in brain and muscle, intermediately expressed in the gills, intestine, heart, and kidney, and weakly expressed in the liver and spleen.