Journal article

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

K Swiderski, KJB Martins, A Chee, J Trieu, T Naim, SM Gehrig, DM Baum, J Brenmoehl, L Chau, R Koopman, P Gregorevic, F Metzger, A Hoeflich, GS Lynch

Growth Hormone and IGF Research | CHURCHILL LIVINGSTONE | Published : 2016

Abstract

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 overexpre..

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Grants

Funding Acknowledgements

This project was supported by the Muscular Dystrophy Association, U.S.A. (GSL). KS was supported by an Early Career Fellowship from the National Health & Medical Research Council of Australia (NH&MRC). The authors thank Professor Jeffrey S. Chamberlain (The University of Washington, Seattle, USA) for provision of the rAAV-CMV-MCS expression vector, and Dr. Hongwei Qian (Baker IDI Heart & Diabetes Institute) for assistance with manufacture of recombinant AAV vectors. The Baker IDI Heart & Diabetes Institute is supported in part by the Operational Infrastructure Support Program of the Victorian Government.