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DOI | 10.1038/s41467-018-03981-8 |
Reducing sarcolipin expression mitigates Duchenne muscular dystrophy and associated cardiomyopathy in mice | |
Voit, Antanina1; 39;Italia, Louis J.2 | |
2017-10-20 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Sarcolipin (SLN) is an inhibitor of the sarco/endoplasmic reticulum (SR) Ca2+ ATPase (SERCA) and is abnormally elevated in the muscle of Duchenne muscular dystrophy (DMD) patients and animal models. Here we show that reducing SLN levels ameliorates dystrophic pathology in the severe dystrophin/utrophin double mutant (mdx: utr(-/-)) mouse model of DMD. Germline inactivation of one allele of the SLN gene normalizes SLN expression, restores SERCA function, mitigates skeletal muscle and cardiac pathology, improves muscle regeneration, and extends the lifespan. To translate our findings into a therapeutic strategy, we knock down SLN expression in 1-month old mdx: utr(-/-) mice via adeno-associated virus (AAV) 9-mediated RNA interference. The AAV treatment markedly reduces SLN expression, attenuates muscle pathology and improves diaphragm, skeletal muscle and cardiac function. Taken together, our findings suggest that SLN reduction is a promising therapeutic approach for DMD. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000413353500017 |
WOS关键词 | TWITCH SKELETAL-MUSCLES ; RETICULUM CA2+ UPTAKE ; MDX MICE ; MESSENGER-RNA ; INTRACELLULAR CALCIUM ; ATRIAL-FIBRILLATION ; PROTEIN EXPRESSION ; DOWN-REGULATION ; GENE-THERAPY ; HEART |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203768 |
专题 | 资源环境科学 |
作者单位 | 1.Rutgers State Univ, Dept Cell Biol & Mol Med, New Jersey Med Sch, Newark, NJ 07103 USA; 2.Rutgers State Univ, New Jersey Med Sch, Dept Pharmacol Physiol & Neurosci, Newark, NJ 07103 USA; 3.Icahn Sch Med Mt Sinai, Cardiovasc Res Ctr, New York, NY 10029 USA; 4.Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA; 5.Birmingham VA Med Ctr, Birmingham, AL 35294 USA; 6.Ohio State Univ, Dept Pediat, Res Inst Nationwide, Childrens Hosp, Columbus, OH 43205 USA; 7.Ohio State Univ, Dept Neurol, Res Inst Nationwide, Childrens Hosp, Columbus, OH 43205 USA; 8.Univ Missouri, Dept Mol Microbiol & Immunol, Neurol, Bioengn,Biomed Sci, Columbia, MO 65212 USA |
推荐引用方式 GB/T 7714 | Voit, Antanina,39;Italia, Louis J.. Reducing sarcolipin expression mitigates Duchenne muscular dystrophy and associated cardiomyopathy in mice[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Voit, Antanina,&39;Italia, Louis J..(2017).Reducing sarcolipin expression mitigates Duchenne muscular dystrophy and associated cardiomyopathy in mice.NATURE COMMUNICATIONS,8. |
MLA | Voit, Antanina,et al."Reducing sarcolipin expression mitigates Duchenne muscular dystrophy and associated cardiomyopathy in mice".NATURE COMMUNICATIONS 8(2017). |
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