Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice

Laura Pelosi, Maria Grazia Berardinelli, Laura Forcina, Elisa Spelta, Emanuele Rizzuto, Carmine Nicoletti, Carlotta Camilli, Erika Testa, Angela Catizone, Fabrizio De Benedetti, Antonio Musarò

Research output: Contribution to journalArticlepeer-review

Abstract

Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy. We report that forced expression of IL-6, in the adult mdx mice, recapitulates the severe phenotypic characteristics of DMD in humans. Increased levels of IL-6 exacerbate the dystrophic muscle phenotype, sustaining inflammatory response and repeated cycles of muscle degeneration and regeneration, leading to exhaustion of satellite cells. The mdx/IL6 mouse closely approximates the human disease and more faithfully recapitulates the disease progression in humans. This study promises to significantly advance our understanding of the pathogenic mechanisms that lead to DMD.

Original languageEnglish
Pages (from-to)6041-6053
Number of pages13
JournalHuman Molecular Genetics
Volume24
Issue number21
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

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