Impaired autophagy correlates with golden retriever muscular dystrophy phenotype Academic Article uri icon

abstract

  • INTRODUCTION: Duchenne muscular dystrophy (DMD) and golden retriever muscular dystrophy (GRMD) are X-linked disorders caused by mutations in the DMD gene. Autophagy was recently identified as a secondary therapeutic target for DMD. We hypothesized that autophagy would be reduced in GRMD. METHODS: Autophagic gene and protein expression was assessed in normal and GRMD skeletal muscles and correlated with phenotypic biomarkers. RESULTS: Muscles were differentially affected. Autophagy gene levels were lower than normal in the GRMD cranial sartorius (CS) but similar in the vastus lateralis (VL). Protein markers of autophagic flux, LC3B-II and p62, were higher in both GRMD muscles, in keeping with impaired autophagy. Protein levels correlated with a more severe phenotype. Autophagic structures were found in necrotic, fast-twitch GRMD myofibers. DISCUSSION: Our data suggest that autophagy is impaired in certain GRMD muscles. Differential GRMD CS involvement emphasizes that therapeutic modulation of autophagy could require specific muscle targeting. Muscle Nerve 58: 418-426, 2018.

author list (cited authors)

  • Stoughton, W. B., Li, J., Balogā€Alvarez, C., & Kornegay, J. N.

citation count

  • 3

publication date

  • April 2018

publisher