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Postnatal PGC‐1α over‐expression improves muscle function in a mouse model of Duchenne muscular dystrophy
Author(s) -
Selsby Joshua T.,
Morine Kevin,
Pendrak Klara,
Tian Z.,
Blanco Erica,
Barton Elisabeth R,
Sweeney H Lee
Publication year - 2009
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.23.1_supplement.600.3
Subject(s) - hindlimb , endocrinology , medicine , skeletal muscle , myosin , duchenne muscular dystrophy , muscular dystrophy , protein subunit , soleus muscle , chemistry , myoglobin , genetically modified mouse , transgene , biochemistry , gene
PGC‐1α has received a great deal of attention due to its potential to induce oxidative and slow proteins. The purpose of this investigation was to: 1) extend observations made in an initial study demonstrating transgenic over‐expression of PGC‐1α reduced dystrophic pathology 2) eliminate effects that could have taken place during development. Neonatal mdx mice were injected in the right hind limb with 1x10 11 gc of AAV causing over‐expression of PGC‐1α and sacrificed at 4 (n=6) or 6 wks of age (n=5). Muscle mass was reduced in limbs over‐expressing PGC‐1α at 4 and 6 wks, however, tetantic force and specific force in the soleus and EDL were either maintained or improved when compared to control limbs. PGC‐1α over‐expression caused EDLs to be more resistant to damage at 6 wks and the soleus to be more fatigue resistant at 4 and 6 wks compared to control limbs. PGC‐1α increased expression of slow proteins as utrophin was increased nearly 2‐fold and type I myosin heavy chain nearly 3‐fold as well as expression of oxidative proteins as cytochrome C and uncoupling protein‐1 were increased approximately 2‐fold, complex IV subunit IV (cytochrome C oxidase) was increased 1.5‐fold and myoglobin was increased 3‐fold in limbs over‐expressing PGC‐1α compared to control limbs. These data demonstrate the potential therapeutic role of the PGC‐1α pathway for dystrophic skeletal muscle. U54‐ AR052646 , F32AR055005‐01, AR053461 , and PPMD.