1. Supraphysiological levels of GDF11 cause atrophy of striated muscle in vivo
Supraphysiological levels of GDF11 cause atrophy of striated muscle in vivo ATwelve‐week‐old male C57BL/6 mice (n = 3) were injected i.p. with PBS (control) or 1 × 1012 gc of a liver‐specific GDF11 packaged in AAV2/8 (AAV8.GDF11), and were euthanized seven days after treatment.B–DImmunoblotting of IgG‐reduced samples (see Materials and Methods) reveals an increase in GDF11 content in AAV8.GDF11‐treated liver (B), serum (C), and quadriceps (D), as detected by the R&D Systems GDF11 mouse mAb under reducing (50 mM DTT) conditions. The identifiable bands of full‐length GDF11 and monomeric GDF11 in the immunoblots are labeled, while an ambiguous 25 kDa band is marked with a star (*). GAPDH immunoblotting is shown to demonstrate equal loading among lanes.E, FSeven days after, AAV8.GDF11 treatment resulted in substantial losses in body weight (E), and muscle mass of the soleus (Sol), extensor digitorum longus (EDL), tibialis anterior (TA), gastrocnemius (Gas), quadriceps (Quad), and heart (F). Values depicted are mean ± SEM. Statistical analysis was performed using two‐tailed Student's t‐test with effect size presented as Cohen's d (d).
David W Hammers et al. EMBO Mol Med. 2017;emmm
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