Skeletal muscle-specific overexpression of IGFBP-2 promotes a slower muscle phenotype in healthy but not dystrophic mdx mice and does not affect the dystrophic pathology

Kristy Swiderski, Karen Janet Bernice Martins, Annabel Chee, Jennifer Trieu, Timur Naim, Stefan Martin Gehrig, Dale Michael Baum, Julia Brenmoehl, Luong Chau, René Koopman, Paul Gregorevic, Friedrich Metzger, Andreas Hoeflich, Gordon Stuart Lynch

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Objective The insulin-like growth factor binding proteins (IGFBPs) are thought to modulate cell size and homeostasis via IGF-I-dependent and -independent pathways. There is a considerable dearth of information regarding the function of IGFBPs in skeletal muscle, particularly their role in the pathophysiology of Duchenne muscular dystrophy (DMD). In this study we tested the hypothesis that intramuscular IGFBP-2 overexpression would ameliorate the pathology in mdx dystrophic mice. Design 4 week old male C57Bl/10 and mdx mice received a single intramuscular injection of AAV6-empty or AAV6-IGFBP-2 vector into the tibialis anterior muscle. At 8 weeks post-injection the effect of IGFBP-2 overexpression on the structure and function of the injected muscle was assessed. Results AAV6-mediated IGFBP-2 overexpression in the tibialis anterior (TA) muscles of 4-week-old C57BL/10 and mdx mice reduced the mass of injected muscle after 8 weeks, inducing a slower muscle phenotype in C57BL/10 but not mdx mice. Analysis of inflammatory and fibrotic gene expression revealed no changes between control and IGFBP-2 injected muscles in dystrophic (mdx) mice. Conclusions Together these results indicate that the IGFBP-2-induced promotion of a slower muscle phenotype is impaired in muscles of dystrophin-deficient mdx mice, which contributes to the inability of IGFBP-2 to ameliorate the dystrophic pathology. The findings implicate the dystrophin-glycoprotein complex (DGC) in the signaling required for this adaptation.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalGrowth Hormone & IGF Research
Publication statusPublished - 1 Oct 2016
Externally publishedYes


  • Dystrophy
  • Fiber type
  • IGFBP-2
  • Muscle
  • Muscle function

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