Myostatin Inhibition Using ActRIIB-mFc Does Not Produce Weight Gain or Strength in the Nebulin Conditional KO Mouse

Jennifer A. Tinklenberg, Emily M. Siebers, Margaret J. Beatka, Brittany A. Fickau, Samuel Ayres, Hui Meng, Lin Yang, Pippa Simpson, Hendrikus "Henk" Granzier, Michael W. Lawlor

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Mutations in at least 12 genes are responsible for a group of congenital skeletal muscle diseases known as nemaline myopathies (NMs). NMs are associated with a range of clinical symptoms and pathological changes often including the presence of cytoplasmic rod-like structures (nemaline bodies) and myofiber hypotrophy. Our recent work has identified a variable degree of behavioral benefit when treating 2 NM mouse models due to mutations in Acta1 with myostatin inhibition. This study is focused on the effects of delivering ActRIIB-mFc (Acceleron; a myostatin inhibitor) to the nebulin conditional knockout KO (Neb cKO) mouse model of NM. Treatment of Neb cKO mice with ActRIIB-mFc did not produce increases in weight gain, strength, myofiber size, or hypertrophic pathway signaling. Overall, our studies demonstrate a lack of response in Neb cKO mice to myostatin inhibition, which differs from the response observed when treating other NM models.

Original languageEnglish (US)
Pages (from-to)130-139
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume78
Issue number2
DOIs
StatePublished - Feb 1 2019

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Tinklenberg, J. A., Siebers, E. M., Beatka, M. J., Fickau, B. A., Ayres, S., Meng, H., Yang, L., Simpson, P., Granzier, H. H., & Lawlor, M. W. (2019). Myostatin Inhibition Using ActRIIB-mFc Does Not Produce Weight Gain or Strength in the Nebulin Conditional KO Mouse. Journal of Neuropathology and Experimental Neurology, 78(2), 130-139. https://doi.org/10.1093/jnen/nly120