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Myostatin blockade improves function but not histopathology in a murine model of limb‐girdle muscular dystrophy 2C
Author(s) -
Bogdanovich Sasha,
McNally Elizabeth M.,
Khurana Tejvir S.
Publication year - 2008
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20920
Subject(s) - myostatin , muscular dystrophy , limb girdle muscular dystrophy , skeletal muscle , blockade , biology , endocrinology , duchenne muscular dystrophy , itga7 , medicine , anatomy , phenotype , genetics , gene , receptor
Myostatin is a negative regulator of skeletal muscle growth. Myostatin mutations and pharmacological strategies increase muscle mass in vivo, suggesting that myostatin blockade may prove useful in diseases characterized by muscle wasting, such as the muscular dystrophies. We subjected the γ‐sarcoglycan–deficient ( Sgcg −/− ) mouse model of limb‐girdle muscular dystrophy (LGMD) 2C to antibody‐mediated myostatin blockade in vivo. Myostatin inhibition led to increased fiber size, muscle mass, and absolute force. However, no clear improvement in muscle histopathology was evident, demonstrating discordance between physiological and histological improvement. These results and previous studies on the dy w / dy w mouse model of congenital muscular dystrophy and in the late‐stage δ‐sarcoglycan–deficient ( Sgcd −/− ) mouse model of LGMD2F document disease‐specific limitations to therapeutic strategies based on myostatin blockade in the more severe mouse models of different muscular dystrophies. Muscle Nerve, 2007