+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Molecular, cellular and physiological investigation of myostatin propeptide-mediated muscle growth in adult mice

Molecular, cellular and physiological investigation of myostatin propeptide-mediated muscle growth in adult mice

Neuromuscular Disorders 19(7): 489-499

Inhibition of myostatin signalling or its biological activity has recently emerged as a potential remedial approach against muscle wasting and degenerative diseases such as muscular dystrophies. In the present study we systemically administered a recombinant AAV8 vector expressing a mutated myostatin propeptide (AAV8ProMyo) to healthy mice in order to assess its impact on the histological, cellular and physiological properties of the skeletal muscle, exploiting the fact that myostatin is naturally inhibited by its own propeptide. We report that a single intravenous administration of AAV8ProMyo leads to increases in muscle mass of tibialis anterior, extensor digitorum longus and gastrocnemius muscles 8 weeks post-injection and tibialis anterior, gastrocnemius and rectus femoris muscles 17 weeks post-injection. Moreover, treatment resulted in muscle fibre hypertrophy but not hyperplasia, with IIB myofibres responding to the greatest extent following propeptide-induced myostatin inhibition. Additionally, myofibre nuclear:cytoplasmic ratio was decreased in the AAV8ProMyo treated animals. Importantly, the hypertrophic EDL muscle 8 weeks after AAV8ProMyo treatment did not show the dramatic decrease in specific force displayed by the germline myostatin null mice.

(PDF emailed within 0-6 h: $19.90)

Accession: 054451344

Download citation: RISBibTeXText

PMID: 19541486

DOI: 10.1016/j.nmd.2009.06.367

Related references

Enhanced muscle growth by plasmid-mediated delivery of myostatin propeptide. Journal of Biomedicine and Biotechnology 2010: 862591, 2010

Muscle-specific transgenic expression of porcine myostatin propeptide enhances muscle growth in mice. Transgenic Research 22(5): 1011-1019, 2014

Coordinated patterns of gene expressions for adult muscle build-up in transgenic mice expressing myostatin propeptide. Bmc Genomics 10: 305, 2009

Propeptide-mediated inhibition of myostatin increases muscle mass through inhibiting proteolytic pathways in aged mice. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 69(9): 1049-1059, 2014

Administration of a mutated myostatin propeptide to neonatal mice significantly enhances skeletal muscle growth. Molecular Reproduction and Development 77(1): 76-82, 2010

Identification of the minimum region of flatfish myostatin propeptide (Pep45-65) for myostatin inhibition and its potential to enhance muscle growth and performance in animals. Plos One 14(4): E0215298, 2019

Myostatin propeptide gene delivery by adeno-associated virus serotype 8 vectors enhances muscle growth and ameliorates dystrophic phenotypes in mdx mice. Human Gene Therapy 19(3): 241-254, 2008

Estradiol in females may negate skeletal muscle myostatin mRNA expression and serum myostatin propeptide levels after eccentric muscle contractions. Journal of Sports Science and Medicine 5(4): 672-681, 2006

Enhanced myogenesis in adult muscle by transgenic expression of myostatin propeptide. Ethnicity and Disease 17(4, Suppl. 5): S63-S64, 2007

Postnatal expression of myostatin propeptide cDNA maintained high muscle growth and normal adipose tissue mass in transgenic mice fed a high-fat diet. Molecular Reproduction and Development 73(4): 462-469, 2006

Myostatin propeptide mutation of the hypermuscular Compact mice decreases the formation of myostatin and improves insulin sensitivity. American Journal of Physiology. Endocrinology and Metabolism 312(3): E150-E160, 2016

Myostatin antisense RNA-mediated muscle growth in normal and cancer cachexia mice. Gene Therapy 15(3): 155-160, 2007

Adeno-associated virus-8-mediated intravenous transfer of myostatin propeptide leads to systemic functional improvements of slow but not fast muscle. Rejuvenation Research 12(2): 85-94, 2009

A myostatin inhibitor (propeptide-Fc) increases muscle mass and muscle fiber size in aged mice but does not increase bone density or bone strength. Experimental Gerontology 48(9): 898-904, 2014

Molecular profiles of Quadriceps muscle in myostatin-null mice reveal PI3K and apoptotic pathways as myostatin targets. Bmc Genomics 10: 196, 2009