Targeted expression of insulin-like growth factor-I reduces early myofiber necrosis in dystrophic mdx mice

Thea Shavlakadze, Jason White, Joseph F.Y. Hoh, Nadia Rosenthal, Miranda D. Grounds

    Research output: Contribution to journalArticle

    85 Citations (Scopus)
    2 Downloads (Pure)

    Abstract

    Necrosis of dystrophic myofibers in Duchenne muscular dystrophy and mdx mice results from defects in the subsarcolemmal protein dystrophin that cause membrane fragility and tears in the sarcolemma, and these lead to the destruction of the myofibers. The present study specifically tests whether overexpression of mIGF-1 in mdx/mIGF-1 transgenic mice reduces myofiber breakdown during the acute onset phase of dystrophy (at 21 days). The extent of muscle damage and Evans blue dye (EBD) staining of myofibers was quantitated histologically for mdx/mIGF-1 and their mdx littermates from 15 to 30 days of age. Overexpression of mIGF-1 strikingly reduced the extent of myofiber damage (histology and EBD staining) by up to 97% in tibialis anterior and quadriceps muscles at 21-22 days after birth. In the mdx diaphragm, the onset of muscle breakdown was earlier (by 15 days after birth) but no significant protective effect of IGF-1 was apparent within the first month of age in mdx/IGF-1 mice. These novel observations show that increased mIGF-1 within mdx myofibers specifically reduces the breakdown of dystrophic muscle during the acute onset of muscle degeneration. This mechanism of action can account for the long-term reduced severity of the dystropathology in mdx mice that overexpress mIGF-1 and provides promising opportunities for therapeutic strategies.
    Original languageEnglish
    Pages (from-to)829-843
    Number of pages15
    JournalMolecular Therapy
    Volume10
    Issue number5
    DOIs
    Publication statusPublished - 01 Nov 2004

    Fingerprint Dive into the research topics of 'Targeted expression of insulin-like growth factor-I reduces early myofiber necrosis in dystrophic mdx mice'. Together they form a unique fingerprint.

  • Cite this