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Characterization of the specific and sustained GH1 expression induced by rAAV2/1 in normal adult male rats

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Abstract

Our aim was to investigate the long-term effects of intramuscular injection of rAAV2/1-CMV-GH1 viral particles on GH1 expression in normal adult male rats. We found that specific and sustained GH1 expression did not improve muscle exercise performance despite inducing local muscle hypertrophy. Injection of rAAV2/1-CMV-GH1 had some systemic effects on the liver and heart and on lipid metabolism in the healthy rats. Serum levels of hGH (human growth hormone), insulin, glucose and leptin increased significantly, which might induce insulin resistance. The serum concentration of IGF-1 (insulin-like growth factor 1), IGF-BP3 (insulin-like growth factor binding protein 3) and PIIINP (N-terminal propeptide of type III procollagen) markedly increased at 24 weeks after injection of GH1. In conclusion, GH1 expression driven by AAV2/1 in normal animals did not improve muscle strength but did increase muscle mass and may have systemic effects in healthy animals.

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Abbreviations

EDL:

Extensor digitorum longus muscle

GH:

Growth hormone

hGH:

Human growth hormone

IGF-1:

Insulin-like growth factor 1

IGF-BP3:

Insulin-like growth factor binding protein 3

MHC:

Myosin heavy chain

PIIINP:

N-terminal propeptide of type III procollagen

rAAV vector:

Recombinant adeno-associated virus vector

rAAV2/1:

Recombinant adeno-associated viral vectors pseudotyped with viral capsids from serotype 1

rtGH:

The replacement therapy of GH

SOL:

Soleus muscle

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Acknowledgments

The authors express gratitude to the staff of the department for their support and suggestions. This work was partly supported by the grants from the National Science Foundation for Post-doctoral Scientists of China to Ying Qin (No. 20080431363) and the National Natural Science Foundation of China to Ya-ping Tian (No. 20635002).

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Chinese PLA General Hospital, 28 Fu-Xing Road, 100853, Beijing, People’s Republic of China

    Ying Qin & Ya-Ping Tian

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  1. Ying Qin
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  2. Ya-Ping Tian
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Correspondence to Ying Qin or Ya-Ping Tian.

Electronic supplementary material

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11033_2010_16_MOESM1_ESM.doc

Table 1. Body weights and organ weights (wet weight) of the rats 24 weeks after the injection of either the rAAV2/1 virus containing the GH1 expression vector, the empty vector or a placebo (saline). * P < 0.05 versus the EV group. (DOC 33 kb)

11033_2010_16_MOESM2_ESM.doc

Table 2. Serum lipid profiles, blood glucose, leptin and insulin 24 weeks after injection. * P < 0.05 and * P < 0.01 versus the EV group. (DOC 32 kb)

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Qin, Y., Tian, YP. Characterization of the specific and sustained GH1 expression induced by rAAV2/1 in normal adult male rats. Mol Biol Rep 37, 3643–3651 (2010). https://doi.org/10.1007/s11033-010-0016-3

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