Affinage

MSTN

Growth/differentiation factor 8 · UniProt O14793

Round 2 corrected
Length
375 aa
Mass
42.8 kDa
Annotated
2026-04-28
130 papers in source corpus 31 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Myostatin (MSTN/GDF8) is a secreted TGF-β superfamily member that functions as a master negative regulator of skeletal muscle mass and additionally suppresses osteogenic, chondrogenic, and adipogenic differentiation. It is synthesized as a precursor that is proteolytically processed into a latent complex of a disulfide-linked C-terminal dimer held noncovalently by the propeptide; activation requires tolloid metalloprotease cleavage of the prodomain at D99, with recognition dependent on Y94 and D92 (PMID:33876824). The active dimer signals primarily through ActRIIB (and ActRIIA), recruiting ALK4 or ALK5 as type I receptors to phosphorylate Smad2/Smad3, which inhibits myoblast differentiation, suppresses the Akt/mTOR/p70S6K protein synthesis axis, and epigenetically maintains hypermethylation of myogenic gene promoters by repressing TET1 transcription (PMID:19357233, PMID:32210722, PMID:14517293). Loss-of-function mutations in MSTN cause dramatic skeletal muscle hypertrophy and hyperplasia in mice, cattle, and humans (PMID:9139826, PMID:9314496, PMID:15215484).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1997 High

    Establishing myostatin as a negative regulator of muscle growth: targeted disruption in mice and natural loss-of-function mutations in cattle independently demonstrated that MSTN loss causes 2–3× increases in skeletal muscle mass through both hyperplasia and hypertrophy, defining the gene's core biological function.

    Evidence Knockout mouse phenotyping (Nature) and cattle breed mutation identification (Genome Research, PNAS)

    PMID:9139826 PMID:9288100 PMID:9314496 PMID:9356471

    Open questions at the time
    • Mechanism of action and receptor identity unknown
    • Relative contribution of hyperplasia vs. hypertrophy unresolved
    • No human validation yet
  2. 2001 High

    Defining the latent complex and receptor system: biochemical studies showed that mature myostatin is a disulfide-linked C-terminal dimer held in an inactive complex by its propeptide, which directly blocks receptor binding; the dimer binds ActRIIB with high affinity and ActRIIA with lower affinity, and transgenic overexpression of the propeptide, follistatin, or dominant-negative ActRIIB phenocopied myostatin knockouts.

    Evidence Protein purification, receptor binding assays, size exclusion chromatography, chemical crosslinking, and transgenic mouse muscle phenotyping

    PMID:11459935 PMID:11519824

    Open questions at the time
    • Type I receptor partners not yet identified
    • Mechanism of latent complex activation unknown
    • Intracellular signaling cascade uncharacterized
  3. 2003 High

    Mapping the intracellular signaling pathway and identifying endogenous serum inhibitors: myostatin was shown to signal through ALK4/ALK5 to phosphorylate Smad2/3, and two additional endogenous inhibitory proteins—FLRG and GASP-1—were identified in serum complexes with myostatin alongside the propeptide, establishing a multi-layered extracellular regulation system.

    Evidence Receptor co-IP, siRNA knockdown, reporter assays, affinity purification/MS from serum, recombinant protein binding

    PMID:12194980 PMID:12595574 PMID:14517293

    Open questions at the time
    • Relative stoichiometric contributions of propeptide, FLRG, GASP-1, and follistatin in vivo unclear
    • Cross-talk with non-Smad pathways not defined
    • Mechanism of latent complex activation still unknown
  4. 2004 High

    Human genetic validation: identification of a loss-of-function MSTN mutation in a child with exceptional muscle hypertrophy confirmed that myostatin's role as a muscle growth inhibitor is conserved in humans.

    Evidence Clinical genetics and MSTN gene sequencing in a hyper-muscular child

    PMID:15215484

    Open questions at the time
    • Only a single human case reported
    • Dose-response and heterozygous phenotype in humans poorly defined
  5. 2009 High

    Dissecting Akt/mTOR suppression as a parallel mechanism: myostatin was shown to inhibit the Akt/mTOR/p70S6K protein synthesis pathway in a Smad2/3-dependent manner, with reciprocal cross-talk whereby TORC1 blockade amplifies Smad2 phosphorylation, explaining myostatin's ability to reduce myotube size independently of atrophy E3 ligases.

    Evidence siRNA knockdown of RAPTOR/RICTOR, phospho-protein immunoblots, myotube diameter measurements

    PMID:19357233

    Open questions at the time
    • Mechanism linking Smad2/3 to Akt suppression not fully resolved
    • In vivo validation of cross-talk incomplete
    • Atrophy-independent fiber size reduction mechanism unclear
  6. 2013 High

    Identifying transcriptional regulation of MSTN itself: NF-κB p65 was shown to bind directly to the myostatin promoter under hyperammonemic conditions, driving transcriptional upregulation—a mechanism linking liver disease–associated sarcopenia to myostatin.

    Evidence ChIP on myostatin promoter, NF-κB siRNA and IKK inhibitor in C2C12 myotubes and mouse hyperammonemia model

    PMID:24145431

    Open questions at the time
    • Other transcriptional regulators of MSTN promoter not systematically identified
    • Whether NF-κB drives MSTN in non-hepatic wasting conditions unknown
  7. 2017 High

    Structural basis for signaling specificity: crystal structures of apo-GDF8 and apo-GDF11 revealed that despite 90% sequence identity, unique features in the type I receptor binding site explain GDF11's higher SMAD2/3 signaling potency, and chimeric mutagenesis confirmed these residues as determinants of signaling output.

    Evidence X-ray crystallography, chimeric mutagenesis, SMAD2/3 phosphorylation assays

    PMID:28257634

    Open questions at the time
    • Full ternary complex structure (ligand–type I–type II) not solved
    • Structural basis for differential receptor recruitment in cells unknown
  8. 2019 High

    Structural mechanism of WFIKKN2 inhibition: crystallography and mutagenesis demonstrated that the WFIKKN2 follistatin domain blocks GDF8 access to ActRIIB through binding contacts distinct from those used by follistatin or FSTL3, revealing non-redundant modes of extracellular antagonism.

    Evidence 1.39 Å crystal structure of WFIKKN2 FSD, SPR, native gel shift, alanine-scanning mutagenesis

    PMID:30814254

    Open questions at the time
    • Full WFIKKN2–GDF8 co-crystal structure not available
    • In vivo contribution of WFIKKN2 vs. other antagonists not quantified
  9. 2020 Medium

    Epigenetic mechanism downstream of Smad signaling: SMAD2/3 occupancy at the TET1 promoter was shown to repress TET1 demethylase transcription, maintaining DNA methylation at myogenic gene promoters (PAX3, PAX7, MyoD, MyoG); MSTN loss derepresses TET1, reducing methylation and promoting differentiation.

    Evidence ChIP-qPCR for SMAD2/3 at TET1 promoter, bisulfite sequencing, TET1 knockdown/overexpression in MSTN+/- satellite cells

    PMID:32210722

    Open questions at the time
    • Single-lab finding awaiting independent replication
    • Whether TET1 regulation is muscle-specific or systemic unknown
    • Contribution relative to direct transcriptional Smad targets not quantified
  10. 2021 High

    Defining prodomain activation mechanism: tolloid metalloproteases were shown to cleave the GDF8 prodomain at D99, with Y94 and D92 identified as critical recognition residues; tolloid-resistant prodomain mutants act as dominant-negative inhibitors.

    Evidence In vitro cleavage assay with Tll1 astacin domain, alanine-scanning mutagenesis, reporter assays

    PMID:33876824

    Open questions at the time
    • In vivo validation of tolloid-dependent activation kinetics missing
    • Structural basis of tolloid–prodomain recognition not solved
    • Alternative activation pathways (e.g., acid pH) not fully characterized
  11. 2025 High

    Demonstrating non-redundancy of GDF8 and activin A: dual antibody blockade of both ligands—but not either alone—fully prevented GLP-1 agonist–induced muscle loss and enhanced fat loss in obese mice and NHPs, establishing GDF8 and activin A as the two principal ActRII ligands limiting muscle mass.

    Evidence Dual antibody blockade in obese mouse and non-human primate models with body composition analysis

    PMID:40360507

    Open questions at the time
    • Relative contribution of each ligand to muscle vs. fat regulation not individually quantified
    • Long-term safety of dual blockade unknown
    • Whether other ActRII ligands contribute in specific disease contexts untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full ternary structure of the GDF8–type I–type II receptor signaling complex, the quantitative in vivo contributions of each extracellular antagonist (propeptide, FLRG, GASP-1, follistatin, WFIKKN2), the complete set of transcriptional regulators of the MSTN promoter beyond NF-κB, and the mechanistic basis for myostatin's non-muscle roles in cardiac, bone, and reproductive tissues.
  • Ternary receptor complex structure unsolved
  • Systematic in vivo dissection of antagonist hierarchy lacking
  • Non-muscle signaling mechanisms poorly defined at molecular level

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 5
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1430728 Metabolism 1
Partners
ACVR1BACVR2AACVR2BFLRGFSTL1FSTL3TGFBR1WFIKKN2
Complex memberships
Latent myostatin complex (propeptide–mature GDF8 dimer)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 GDF-8 (myostatin) is expressed specifically in developing and adult skeletal muscle; targeted disruption in mice causes a large and widespread increase in skeletal muscle mass (2–3× per muscle), resulting from both muscle cell hyperplasia and hypertrophy, establishing myostatin as a negative regulator of skeletal muscle growth. Gene targeting / knockout mouse, muscle weight measurements, histology Nature High 9139826
1997 Loss-of-function mutations in the myostatin coding sequence (11-bp deletion causing frameshift in Belgian Blue; C→Y missense in conserved cysteine in Piedmontese) underlie the double-muscled phenotype in cattle, confirming myostatin as a negative regulator of muscle mass in cattle. cDNA cloning, sequence analysis of normal and double-muscled cattle, expression profiling Genome research / PNAS High 9288100 9314496 9356471
2001 Mature myostatin protein consists of a noncovalently held complex of the N-terminal propeptide and a disulfide-linked C-terminal dimer; the C-terminal dimer binds the activin type II receptors ActRIIB (high affinity) and ActRIIA (lower affinity). Transgenic overexpression of the propeptide, follistatin, or a dominant-negative ActRIIB in skeletal muscle each produce dramatic muscle mass increases comparable to myostatin knockouts, establishing these as functional inhibitors of the pathway in vivo. Protein purification from mammalian cells, receptor binding assays, transgenic mouse overexpression with muscle mass phenotyping PNAS High 11459935
2001 The GDF-8 propeptide forms a noncovalent complex with mature GDF-8 (shown by size exclusion chromatography and chemical crosslinking), inhibits GDF-8 biological activity in a reporter-gene assay, and blocks specific GDF-8 binding to L6 myoblast cells, identifying the propeptide as a direct inhibitor that acts by preventing receptor binding. Size exclusion chromatography, chemical crosslinking, cell-based reporter assay, radioligand receptor-binding competition Growth factors High 11519824
2002 Circulating myostatin in normal mouse and human serum is bound in latent complexes with at least two major inhibitory proteins: the myostatin propeptide (accounting for >70% of serum myostatin) and the follistatin-related gene product FLRG. FLRG was confirmed to bind mature myostatin directly and inhibit its activity in a reporter assay. Affinity purification with anti-myostatin monoclonal antibody, mass spectrometry, Western blot, recombinant protein binding, luciferase reporter assay Journal of Biological Chemistry High 12194980
2003 Myostatin signals via ActRIIB as the primary type II receptor, then partners with ALK4 (ActRIB) or ALK5 (TβRI) as type I receptors to phosphorylate Smad2/Smad3, activating a TGF-β-like pathway. Myostatin inhibits BMP7- but not BMP2-mediated adipogenic differentiation by competing for ActRIIB, thereby blocking adipogenesis. Receptor binding assays, reporter gene assays, co-immunoprecipitation, siRNA knockdown, BMP competition binding Molecular and Cellular Biology High 14517293
2003 GASP-1 (growth and differentiation factor-associated serum protein-1), containing whey acidic protein, Kazal, two Kunitz, netrin, and follistatin-like domains, is identified as an endogenous serum-binding protein of myostatin. GASP-1 binds both mature myostatin and the myostatin propeptide directly and inhibits mature myostatin biological activity but not activin activity. Affinity purification from serum, mass spectrometry, recombinant protein binding, luciferase reporter assay Molecular Endocrinology High 12595574
2003 GDF-8 treatment of porcine embryonic myogenic cells suppresses proliferation and increases IGFBP-3 protein and mRNA production; a neutralizing anti-IGFBP-3 antibody partially rescues GDF-8-induced proliferation suppression, indicating IGFBP-3 mediates part of GDF-8's anti-proliferative effect in myogenic cells. Cell proliferation assay, ELISA/immunoblot for IGFBP-3, antibody neutralization Journal of Cellular Physiology Medium 14502562
2004 A child with exceptional muscle hypertrophy was found to carry a mutation in the human MSTN gene, demonstrating that myostatin regulates muscle mass in humans. Clinical genetics, sequencing of human MSTN gene in patient New England Journal of Medicine High 15215484
2009 Myostatin inhibits activation of the Akt/mTOR/p70S6K protein synthesis pathway in myoblasts and myotubes, requiring Smad2 and Smad3 downstream of ActRII/ALK receptors. Blockade of RAPTOR (TORC1 component) amplifies myostatin-induced Smad2 phosphorylation, establishing a cross-talk whereby Akt suppression by myostatin feeds back to enhance Smad signaling. Myostatin decreases myotube diameter without upregulating atrophy E3 ligases MuRF1/MAFbx, instead suppressing differentiation-associated genes. siRNA knockdown of RAPTOR/RICTOR, phospho-protein immunoblot, myotube diameter measurement, gene expression American Journal of Physiology – Cell Physiology High 19357233
1998 The human myostatin gene comprises three exons and two introns, maps to chromosomal region 2q33.2, is transcribed as a 3.1-kb mRNA encoding a 375-aa precursor protein, and is expressed in skeletal muscle as a secreted 26-kDa mature glycoprotein detectable in plasma. Serum and intramuscular myostatin concentrations are elevated in HIV-infected men with weight loss and correlate inversely with fat-free mass, implicating myostatin in human muscle wasting. Molecular cloning, RT-PCR, Western blot, immunohistochemistry, ELISA PNAS High 9843994
1999 Myostatin mRNA and protein are expressed not only in skeletal muscle but also in fetal and adult heart tissue, with protein localized to Purkinje fibers and cardiomyocytes; myostatin expression is upregulated in cardiomyocytes surrounding the infarct zone after myocardial infarction, suggesting a role in cardiac physiology. RT-PCR, Western blot, immunohistochemistry on heart sections, myocardial infarction model Journal of Cellular Physiology Medium 10362012
2013 Hyperammonemia (as occurs in liver cirrhosis) induces myostatin expression in skeletal muscle via an NF-κB-dependent mechanism: ammonia activates IκB kinase, triggers NF-κB nuclear translocation, and the NF-κB p65 subunit binds specific sites in the myostatin promoter to drive transcription. Pharmacologic inhibition or gene silencing of NF-κB abolishes this upregulation. C2C12 myotube ammonium acetate treatment, NF-κB ChIP, siRNA knockdown, IKK inhibitor, primary muscle cell cultures, in vivo mouse hyperammonemia model PNAS High 24145431
2017 Despite 90% amino acid sequence identity, GDF11 is a more potent activator of SMAD2/3 and signals more effectively through ALK4/5/7 than GDF8. Crystal structures of the GDF11:FS288 complex, apo-GDF8, and apo-GDF11 reveal unique structural features in the type I receptor binding site of each ligand; substitution of GDF11 residues into GDF8 confers enhanced SMAD2/3 signaling activity to GDF8. Crystal structure determination, SMAD2/3 phosphorylation assays, chimeric protein mutagenesis, receptor signaling assays BMC Biology High 28257634
2019 The WFIKKN2 follistatin domain (FSD) directly binds GDF8 and GDF11 and blocks their interaction with the type II receptor ActRIIB (shown by native gel shift and surface plasmon resonance). Crystal structure of the WFIKKN2 FSD at 1.39 Å identified surface-exposed residues that, when mutated to alanine, reduce GDF8 antagonism in full-length WFIKKN2. The WFIKKN2 FSD inhibits GDF8 via different binding contacts than follistatin or FSTL3. Protein crystallography (1.39 Å), surface plasmon resonance, native gel shift, alanine-scanning mutagenesis, functional antagonism assay Journal of Biological Chemistry High 30814254
2021 Tolloid-family metalloproteases activate latent GDF8 by cleaving the prodomain at residue D99. Sequential alanine mutagenesis identified Y94 and D92 as critical residues adjacent to the scissile bond for tolloid recognition; D92A and Y94A mutations impede tolloid-mediated cleavage but allow full activation under acidic conditions. Co-expression of tolloid-resistant prodomain mutants with wild-type GDF8 suppresses GDF8 activity in a dominant-negative manner. Alanine-scanning mutagenesis of GDF8 prodomain, in vitro protease cleavage assays using astacin domain of Tll1, latent complex purification, reporter assay Biochemical Journal High 33876824
2014 The small molecules dorsomorphin and LDN-193189 inhibit GDF8/myostatin signaling by binding the type II receptor ActRIIA (crystal structure of ActRIIA:dorsomorphin solved), blocking GDF8-induced Smad2/3 phosphorylation and repression of myogenic transcription factors, thereby rescuing myoblast differentiation and promoting contractile myotubular network activity. Crystal structure determination of ActRIIA:dorsomorphin, Smad2/3 phosphorylation assays, myoblast differentiation assays, quantitative live-cell microscopy Journal of Biological Chemistry High 25368322
2020 In MSTN mutant (MSTN-/+) satellite cells, SMAD2/SMAD3 complex binding to the TET1 promoter normally represses TET1 transcription. Loss of MSTN signaling reduces SMAD2/SMAD3 occupancy at the TET1 promoter (shown by ChIP-qPCR), increasing TET1 demethylase expression and reducing DNA methylation of PAX3, PAX7, MyoD, and MyoG promoters/gene bodies, thereby promoting myogenic differentiation. ChIP-qPCR, bisulfite sequencing (methylation analysis), TET1 overexpression and knockdown, myotube fusion index International Journal of Biological Sciences Medium 32210722
2020 GDF8 upregulates SERPINE1 (PAI-1) expression in human granulosa-lutein cells via the ALK5-mediated SMAD2/3-SMAD4 signaling pathway (not via ERK1/2, which is also activated but is not required for SERPINE1 induction), and requires TP53; this SERPINE1 upregulation mediates GDF8-induced glucose metabolism defects. siRNA knockdown of ALK5, SMAD2, SMAD3, ERK1/2, TP53; pharmacological inhibitor SB-431542; transcriptome sequencing; DHEA-induced PCOS mouse model Molecular Therapy – Nucleic Acids Medium 33425488
2020 GDF8 upregulates FSTL3 expression in human extravillous cytotrophoblast cells via the ALK5-SMAD2/3 signaling pathway, and this FSTL3 induction promotes trophoblast cell invasiveness; siRNA knockdown of ALK5 or SMAD2/3 abolishes the effect. siRNA knockdown, immunoblot, invasion assay (Matrigel), pharmacological inhibitor Frontiers in Cell and Developmental Biology Medium 33195207
2021 GDF-8 upregulates MMP2 (but not MMP9) expression in human extravillous cytotrophoblast (HTR-8/SVneo) cells via the ALK5-SMAD2/3 signaling pathway; knockdown of MMP2 attenuates GDF-8-induced cell invasiveness, linking the ALK5-SMAD2/3-MMP2 axis to trophoblast invasion. siRNA knockdown of ALK5, SMAD2/3, MMP2; immunoblot; invasion assay Reproduction Medium 34432647
2021 GDF-8 stimulates aromatase (CYP19A1) expression and estradiol production in human granulosa-lutein cells via ALK5-mediated SMAD2/3 signaling; pharmacological blockade of ALK5 with SB431542 alleviates ovarian hyperstimulation syndrome symptoms and aromatase upregulation in a rat OHSS model. In vitro granulosa cell treatment, siRNA knockdown of ALK5/SMAD2/3, rat OHSS model, SB431542 pharmacological inhibition, ELISA International Journal of Biological Sciences Medium 34239360
2019 GDF8 activates p38 MAPK signaling in cumulus cells and oocytes during in vitro maturation of porcine oocytes, acting through ActRIIb and Alk4/5 receptors; p38 MAPK phosphorylation alters downstream gene expression (Nrf2, Bcl-2, Has2, Ptx3, TNFAIP6) and reduces intracellular ROS, improving oocyte quality and embryo developmental competence. Receptor gene transcription assay, phospho-p38 immunoblot, gene expression analysis, ROS measurement, IVF/PA developmental assay Theriogenology Medium 28708509
2019 MSTN attenuates pathological cardiac hypertrophy and excessive autophagy by directly inactivating AMPK/mTOR signaling and activating PPARγ/NF-κB signaling; additionally, MSTN downregulates miR-128 expression (induced by pressure overload/Ang II), preventing miR-128-mediated suppression of its target PPARγ, thereby maintaining the PPARγ/NF-κB axis. Myostatin knockout (MSTN-/-) mice, abdominal aorta coarctation model, Ang II treatment in vitro and in vivo, AMPK/mTOR/PPARγ/NF-κB pathway immunoblots, miR-128 overexpression/inhibition Molecular Therapy – Nucleic Acids Medium 31923740
2014 Suppression of myostatin by an anti-MSTN polyclonal antibody in diet-induced obese rats reverses insulin resistance by enhancing PI3K activity, Akt phosphorylation, GLUT4 expression, and mTOR phosphorylation, while inhibiting FoxO1 phosphorylation, without affecting GSK-3β phosphorylation, defining MSTN/PI3K/Akt/mTOR and MSTN/PI3K/Akt/FoxO1 as relevant signaling axes. Anti-MSTN antibody treatment in obese rats, PI3K activity assay, phospho-protein immunoblots, GLUT4 protein expression Biotechnology Letters Medium 25048241
2025 Dual blockade of GDF8 and activin A (the two major ActRIIA/B ligands mediating muscle minimization) prevents GLP-1 receptor agonist-induced muscle loss and increases muscle mass in obese mice and non-human primates; this muscle preservation additionally enhances fat loss, demonstrating that GDF8 and activin A together are the principal ligands through which the ActRII receptor pathway reduces muscle mass. Dual antibody blockade in obese mouse and NHP models, body composition analysis (muscle/fat mass), GLP-1 agonist co-treatment Nature Communications High 40360507
2008 Myostatin deficiency leads to increased osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro; BMSCs express the myostatin receptor AcvrIIB, and recombinant myostatin decreases expression of osteogenic factors BMP-2 and IGF-1 in mechanically loaded BMSCs. This osteogenic advantage is abolished by unloading, indicating myostatin suppresses mechanosensitivity-dependent osteogenic factor expression. BMSC isolation from myostatin-null mice, osteogenic differentiation assays, immunofluorescence for AcvrIIB, recombinant myostatin treatment, hindlimb unloading model Bone Medium 17383950
2011 Myostatin treatment of bone marrow stromal cells (BMSCs) and epiphyseal growth plate chondrocytes inhibits their proliferation; myostatin suppresses chondrogenic differentiation of BMSCs by reducing collagen type II synthesis and significantly downregulating Sox9 mRNA expression, establishing a direct inhibitory role for myostatin in chondrogenesis. Proliferation assays on myostatin-deficient mouse BMSCs and chondrocytes, recombinant myostatin treatment, collagen type II ELISA, real-time PCR for Sox9 Growth Factors Medium 21756198
2020 A single amino acid deletion in the MSTN propeptide region (deletion of cysteine 42, caused by a 3-bp deletion in exon 1) is sufficient to produce muscle hyperplasia (increased fiber number) without hypertrophy, and reduces fat pad weight in homozygous quail, demonstrating that cysteine 42 in the propeptide is functionally important for MSTN activity in avian species. CRISPR/Cas9 adenoviral gene editing in quail, genotyping, histology, body composition analysis International Journal of Molecular Sciences Medium 32098368

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 3085 9139826
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1997 Double muscling in cattle due to mutations in the myostatin gene. Proceedings of the National Academy of Sciences of the United States of America 1400 9356471
2001 Regulation of myostatin activity and muscle growth. Proceedings of the National Academy of Sciences of the United States of America 1239 11459935
1997 A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nature genetics 1036 9288100
2004 Myostatin mutation associated with gross muscle hypertrophy in a child. The New England journal of medicine 1019 15215484
1997 Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattle. Genome research 844 9314496
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2009 Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. American journal of physiology. Cell physiology 600 19357233
2003 Myostatin signals through a transforming growth factor beta-like signaling pathway to block adipogenesis. Molecular and cellular biology 450 14517293
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1998 Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proceedings of the National Academy of Sciences of the United States of America 437 9843994
2011 Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature 405 22020285
2007 Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle. Journal of applied physiology (Bethesda, Md. : 1985) 371 17823296
2002 The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum. The Journal of biological chemistry 368 12194980
2000 The family of bone morphogenetic proteins. Kidney international 353 10844590
2012 Strength training with blood flow restriction diminishes myostatin gene expression. Medicine and science in sports and exercise 319 21900845
1999 Myostatin, a transforming growth factor-beta superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct. Journal of cellular physiology 314 10362012
1996 Activation of signalling by the activin receptor complex. Molecular and cellular biology 296 8622651
2008 Increased secretion and expression of myostatin in skeletal muscle from extremely obese women. Diabetes 252 18835929
1995 Comparative genome map of human and cattle. Genomics 244 7558031
2013 Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB-mediated mechanism. Proceedings of the National Academy of Sciences of the United States of America 229 24145431
2008 Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation. Rejuvenation research 219 18240972
1999 Myostatin and the control of skeletal muscle mass. Current opinion in genetics & development 208 10508689
2001 GDF-8 propeptide binds to GDF-8 and antagonizes biological activity by inhibiting GDF-8 receptor binding. Growth factors (Chur, Switzerland) 206 11519824
2016 Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease. Cell metabolism 176 27304512
2003 Regulation of myostatin in vivo by growth and differentiation factor-associated serum protein-1: a novel protein with protease inhibitor and follistatin domains. Molecular endocrinology (Baltimore, Md.) 174 12595574
2016 Biochemistry and Biology of GDF11 and Myostatin: Similarities, Differences, and Questions for Future Investigation. Circulation research 169 27034275
2010 Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. Journal of musculoskeletal & neuronal interactions 166 20190380
2017 Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis. Journal of cachexia, sarcopenia and muscle 159 28627027
2014 Myostatin and sarcopenia: opportunities and challenges - a mini-review. Gerontology 150 24457615
2010 A sequence polymorphism in MSTN predicts sprinting ability and racing stamina in thoroughbred horses. PloS one 144 20098749
2007 Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading. Bone 144 17383950
2007 Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle. American journal of physiology. Endocrinology and metabolism 139 17609255
2015 Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system. Scientific reports 133 26354037
2006 GRB14, GPD1, and GDF8 as potential network collaborators in weight loss-induced improvements in insulin action in human skeletal muscle. Physiological genomics 112 16849634
2010 A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses. BMC genomics 109 20932346
2017 Structural basis for potency differences between GDF8 and GDF11. BMC biology 95 28257634
1999 Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes. Genomics 89 10610713
2001 Polymorphic variation in the human myostatin (GDF-8) gene and association with strength measures in the Women's Health and Aging Study II cohort. Journal of the American Geriatrics Society 76 11555072
2008 Myostatin (GDF-8) deficiency increases fracture callus size, Sox-5 expression, and callus bone volume. Bone 70 18852073
2007 Evidence for multiple alleles effecting muscling and fatness at the ovine GDF8 locus. BMC genetics 64 17996073
2020 GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone. Proceedings of the National Academy of Sciences of the United States of America 58 32071240
2008 Two single nucleotide polymorphisms in the myostatin (GDF8) gene have significant association with muscle depth of commercial Charollais sheep. Animal genetics 58 18462481
2014 Efficient generation of myostatin (MSTN) biallelic mutations in cattle using zinc finger nucleases. PloS one 57 24743319
2016 Isozygous and selectable marker-free MSTN knockout cloned pigs generated by the combined use of CRISPR/Cas9 and Cre/LoxP. Scientific reports 55 27530319
2007 Myostatin (MSTN) gene duplications in Atlantic salmon (Salmo salar): evidence for different selective pressure on teleost MSTN-1 and -2. Gene 50 17890020
2018 CRISPR/Cas9-mediated MSTN disruption and heritable mutagenesis in goats causes increased body mass. Animal genetics 47 29446146
2014 Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation. The Journal of biological chemistry 47 25368322
2020 Muscle Hyperplasia in Japanese Quail by Single Amino Acid Deletion in MSTN Propeptide. International journal of molecular sciences 45 32098368
2019 MSTN Attenuates Cardiac Hypertrophy through Inhibition of Excessive Cardiac Autophagy by Blocking AMPK /mTOR and miR-128/PPARγ/NF-κB. Molecular therapy. Nucleic acids 45 31923740
2017 Inhibition of GDF8 (Myostatin) accelerates bone regeneration in diabetes mellitus type 2. Scientific reports 42 28852138
2010 Impact of two myostatin (MSTN) mutations on weight gain and lamb carcass classification in Norwegian White Sheep (Ovis aries). Genetics, selection, evolution : GSE 42 20113462
2005 Effects of the compact mutant myostatin allele Mstn (Cmpt-dl1Abc) introgressed into a high growth mouse line on skeletal muscle cellularity. Journal of muscle research and cell motility 40 16003464
2021 Production of MSTN-mutated cattle without exogenous gene integration using CRISPR-Cas9. Biotechnology journal 37 34247443
2020 MSTN Mutant Promotes Myogenic Differentiation by Increasing Demethylase TET1 Expression via the SMAD2/SMAD3 Pathway. International journal of biological sciences 35 32210722
2011 Myostatin (GDF-8) inhibits chondrogenesis and chondrocyte proliferation in vitro by suppressing Sox-9 expression. Growth factors (Chur, Switzerland) 35 21756198
2009 Investigations into the GDF8 g+6723G-A polymorphism in New Zealand Texel sheep. Journal of animal science 35 19251921
2012 Immunolocalization of myostatin (GDF-8) following musculoskeletal injury and the effects of exogenous myostatin on muscle and bone healing. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 34 22205678
2005 A directed search in the region of GDF8 for quantitative trait loci affecting carcass traits in Texel sheep. Journal of animal science 33 16100053
2021 Long-term, multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production. Science China. Life sciences 32 34109474
2014 The A55T and K153R polymorphisms of MSTN gene are associated with the strength training-induced muscle hypertrophy among Han Chinese men. Journal of sports sciences 32 24479661
2011 Polymorphisms of myostatin gene (MSTN) in four goat breeds and their effects on Boer goat growth performance. Molecular biology reports 32 21710248
2020 CRISPR/Cas9-mediated MSTN disruption accelerates the growth of Chinese Bama pigs. Reproduction in domestic animals = Zuchthygiene 31 32679613
2010 Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency. European journal of human genetics : EJHG 31 20648054
2003 Mapping modifiers affecting muscularity of the myostatin mutant (Mstn(Cmpt-dl1Abc)) compact mouse. Genetics 31 14504233
2020 Aberrant elevation of GDF8 impairs granulosa cell glucose metabolism via upregulating SERPINE1 expression in patients with PCOS. Molecular therapy. Nucleic acids 30 33425488
2019 Comparison of gene editing efficiencies of CRISPR/Cas9 and TALEN for generation of MSTN knock-out cashmere goats. Theriogenology 30 30981084
2018 CRISPR/Cas9-mediated sheep MSTN gene knockout and promote sSMSCs differentiation. Journal of cellular biochemistry 30 30242885
2017 GDF8 inhibits bone formation and promotes bone resorption in mice. Clinical and experimental pharmacology & physiology 30 28074479
2016 Establishment and phenotypic analysis of an Mstn knockout rat. Biochemical and biophysical research communications 30 27289021
2009 Myostatin (GDF8) single nucleotide polymorphisms in Nellore cattle. Genetics and molecular research : GMR 30 19731204
2025 GDF8 and activin A blockade protects against GLP-1-induced muscle loss while enhancing fat loss in obese male mice and non-human primates. Nature communications 29 40360507
2019 IMB0901 inhibits muscle atrophy induced by cancer cachexia through MSTN signaling pathway. Skeletal muscle 29 30922397
2019 Proteomics insights into the effects of MSTN on muscle glucose and lipid metabolism in genetically edited cattle. General and comparative endocrinology 27 31374285
2011 Analysis of the single-nucleotide polymorphism in the 5'UTR and part of intron I of the sheep MSTN gene. DNA and cell biology 27 21323579
2003 Role of insulin-like growth factor binding protein (IGFBP)-3 in TGF-beta- and GDF-8 (myostatin)-induced suppression of proliferation in porcine embryonic myogenic cell cultures. Journal of cellular physiology 27 14502562
2012 Molecular characterization of myostatin (MSTN) gene and association analysis with growth traits in the bighead carp (Aristichthys nobilis). Molecular biology reports 26 22714921
2020 Effective MSTN Gene Knockout by AdV-Delivered CRISPR/Cas9 in Postnatal Chick Leg Muscle. International journal of molecular sciences 25 32276422
2018 CRISPR/Cas9-mediated specific integration of fat-1 at the goat MSTN locus. The FEBS journal 25 29802684
2007 Characterization of amphioxus GDF8/11 gene, an archetype of vertebrate MSTN and GDF11. Development genes and evolution 25 17551751
2019 Prevalence of DLL3, CTLA-4 and MSTN Expression in Patients with Small Cell Lung Cancer. OncoTargets and therapy 24 31819500
2022 Optimized Cas9:sgRNA delivery efficiently generates biallelic MSTN knockout sheep without affecting meat quality. BMC genomics 23 35524183
2019 Inefficient ATP synthesis by inhibiting mitochondrial respiration causes lipids to decrease in MSTN-lacking muscles of loach Misgurnus anguillicaudatus. Functional & integrative genomics 23 31134482
2020 Myostatin (MSTN) Gene Indel Variation and Its Associations with Body Traits in Shaanbei White Cashmere Goat. Animals : an open access journal from MDPI 22 31963797
2020 Effect of MSTN Mutation on Growth and Carcass Performance in Duroc x Meishan Hybrid Population. Animals : an open access journal from MDPI 22 32481564
2017 GDF8 activates p38 MAPK signaling during porcine oocyte maturation in vitro. Theriogenology 21 28708509
2010 Age-related changes in craniofacial morphology in GDF-8 (myostatin)-deficient mice. Anatomical record (Hoboken, N.J. : 2007) 21 19899116
2009 An insertion in the coding region of the myostatin (MSTN) gene affects carcass conformation and fatness in the Norwegian Spaelsau (Ovis aries). BMC research notes 21 19505313
2020 Exogenous GDF11, but not GDF8, reduces body weight and improves glucose homeostasis in mice. Scientific reports 20 32165710
2013 Targeted disruption of the sheep MSTN gene by engineered zinc-finger nucleases. Molecular biology reports 20 24197697
2011 A promoter polymorphism of MSTN g.-371T>A and its associations with carcass traits in Korean cattle. Molecular biology reports 20 21743995
2020 GDF8 Promotes the Cell Invasiveness in Human Trophoblasts by Upregulating the Expression of Follistatin-Like 3 Through the ALK5-SMAD2/3 Signaling Pathway. Frontiers in cell and developmental biology 19 33195207
2019 The contribution of myostatin (MSTN) and additional modifying genetic loci to race distance aptitude in Thoroughbred horses racing in different geographic regions. Equine veterinary journal 19 30604488
2019 Inhibition of MSTN signal pathway may participate in LIPUS preventing bone loss in ovariectomized rats. Journal of bone and mineral metabolism 19 31414284
2022 Germline transmission of MSTN knockout cattle via CRISPR-Cas9. Theriogenology 18 36037573
2019 Growth Differentiation Factor-8 (GDF8)/Myostatin is a Predictor of Troponin I Peak and a Marker of Clinical Severity after Acute Myocardial Infarction. Journal of clinical medicine 18 31906236
2013 Polymorphisms of the myostatin gene (MSTN) and its relationship with growth traits in goat breeds. Genetics and molecular research : GMR 18 23613242
2020 Mutation in myostatin 3'UTR promotes C2C12 myoblast proliferation and differentiation by blocking the translation of MSTN. International journal of biological macromolecules 17 32156541
2019 Expression of MSTN gene and its correlation with pectoralis muscle fiber traits in the domestic pigeons (Columba livia). Poultry science 17 31265735
2017 Interaction with the GDF8/11 pathway reveals treatment options for adenocarcinoma of the breast. Breast (Edinburgh, Scotland) 17 29156385
2008 Mammary gland differentiation inversely correlates with GDF-8 expression. Molecular reproduction and development 17 18389502
2024 A MSTNDel73C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia. eLife 16 39365728
2021 GDF-8 stimulates trophoblast cell invasion by inducing ALK5-SMAD2/3-mediated MMP2 expression. Reproduction (Cambridge, England) 16 34432647
2013 Genetic variations in the myostatin gene (MSTN) in New Zealand sheep breeds. Molecular biology reports 16 24081623
2019 Crystal structure of the WFIKKN2 follistatin domain reveals insight into how it inhibits growth differentiation factor 8 (GDF8) and GDF11. The Journal of biological chemistry 15 30814254
2017 The Effect of Myostatin (GDF-8) on Proliferation and Tenocyte Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells. The journal of hand surgery Asian-Pacific volume 15 28506172
2016 Quantitative measurements of GDF-8 using immunoaffinity LC-MS/MS. Proteomics. Clinical applications 15 26846723
2012 Assessment of tools for marker-assisted selection in a marine commercial species: significant association between MSTN-1 gene polymorphism and growth traits. TheScientificWorldJournal 15 22666112
2009 Characterization of myostatin/gdf8/11 in the starlet sea anemone Nematostella vectensis. Journal of experimental zoology. Part B, Molecular and developmental evolution 15 19533681
2019 GDF8 enhances SOX2 expression and blastocyst total cell number in porcine IVF embryo development. Theriogenology 14 30825707
2018 Effects of fasting and re-feeding on mstn and mstnb genes expressions in Cranoglanis bouderius. Gene 14 30267811
2014 A new single nucleotide polymorphism in the rabbit (Oryctolagus cuniculus) myostatin (MSTN) gene is associated with carcass composition traits. Animal genetics 14 24796976
2014 A prepared anti-MSTN polyclonal antibody reverses insulin resistance of diet-induced obese rats via regulation of PI3K/Akt/mTOR&FoxO1 signal pathways. Biotechnology letters 14 25048241
2022 MSTN Regulatory Network in Mongolian Horse Muscle Satellite Cells Revealed with miRNA Interference Technologies. Genes 13 36292721
2019 Label-Free LC-MS/MS Proteomics Analyses Reveal Proteomic Changes Accompanying MSTN KO in C2C12 Cells. BioMed research international 13 31073529
2014 Analysis of the 227 bp short interspersed nuclear element (SINE) insertion of the promoter of the myostatin (MSTN) gene in different horse breeds. Veterinaria italiana 13 25273961
2008 A retrovirus-based system to stably silence GDF-8 expression and enhance myogenic differentiation in human rhabdomyosarcoma cells. The journal of gene medicine 13 18563849
2002 Identification of three SNPs in the porcine myostatin gene (MSTN). Animal biotechnology 13 12212941
2023 Resistance exercise alleviates dexamethasone-induced muscle atrophy via Sestrin2/MSTN pathway in C57BL/6J mice. Experimental cell research 12 37709247
2021 A highly prevalent SINE mutation in the myostatin (MSTN) gene promoter is associated with low circulating myostatin concentration in Thoroughbred racehorses. Scientific reports 12 33846367
2021 High ovarian GDF-8 levels contribute to elevated estradiol production in ovarian hyperstimulation syndrome by stimulating aromatase expression. International journal of biological sciences 12 34239360
2019 Targeting Unique Epitopes on Highly Similar Proteins GDF-11 and GDF-8 with Modified DNA Aptamers. Biochemistry 12 31638376
2013 Characterization of myostatin gene (MSTN) of Pekin duck and the association of its polymorphism with breast muscle traits. Genetics and molecular research : GMR 12 23479163
2019 Significant body mass increase by oral administration of a cascade of shIL21-MSTN yeast-based DNA vaccine in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 31302418
2019 Increasing the accuracy of genomic prediction in pure-bred Limousin beef cattle by including cross-bred Limousin data and accounting for an F94L variant in MSTN. Animal genetics 11 31486116
2022 Differential Expression of MSTN Isoforms in Muscle between Broiler and Layer Chickens. Animals : an open access journal from MDPI 10 35268106
2014 Characterization of 5' upstream region and investigation of TTTTA deletion in 5' UTR of myostatin (MSTN) gene in Indian goat breeds. Animal biotechnology 10 24299184
2021 Characterization of tolloid-mediated cleavage of the GDF8 procomplex. The Biochemical journal 9 33876824