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Postnatal PGC‐1α gene transfer attenuates acute injury in mdx mice
Author(s) -
Selsby Joshua T,
GardanSalmon Delphine
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.987.8
Subject(s) - dystrophin , utrophin , duchenne muscular dystrophy , muscular dystrophy , skeletal muscle , medicine , endocrinology
A promising strategy to treat Duchenne muscular dystrophy aims to replace the aberrant dystrophin protein with utrophin, a dystrophin related‐protein. Induction of PGC‐1α increases utrophin and may also support damaged mitochondria. Previously, constitutive PGC‐1α over‐expression reduced acute injury in dystrophic skeletal muscle. As dystrophin deficiency results in developmental abnormalities potentially improved by constitutive PGC‐1α over‐expression, it is imperative to determine the extent to which post‐natal PGC‐1α over‐expression prevents acute injury in dystrophic muscle. Neonatal mdx mice were injected in the right limb with 1×10 11 gc of AAV 2/6 causing over‐expression of PGC‐1α while the left was injected with null virus. At 6 weeks of age, mice performed downhill running (−17°, 10m/min for one hour) to cause an acute eccentric injury, and were sacrificed 72 hours later. Following injury, PGC‐1α over‐expression in the soleus caused a 50% reduction in necrotic area and Evan's blue dye penetration (p<0.05), and tended to reduce central nucleation when compared to contralateral control muscle. These data indicate that PGC‐1α gene transfer following in utero development protects dystrophic muscle from acute injury.