Myostatin Mutation Associated with Gross Muscle Hypertrophy in a Child

作者：Markus Schuelke, Kathryn R. Wagner, Leslie E. Stolz, Christoph Hübner, T Riebel, Wolfgang Kömen, Thomas W Braun, James F. Tobin, Se‐Jin Lee · 发表于：New England Journal of Medicine · 年份：2004 · DOI：10.1056/nejmoa040933 · 被引用次数：1403 · 研究领域：Muscle Physiology and Disorders、Cardiomyopathy and Myosin Studies、Neurogenetic and Muscular Disorders Research

uscle wasting and weakness are among the most common inherited and acquired disorders and include the muscular dystrophies, cachexia, and age-related wasting.Since there is no generally accepted treatment to improve muscle bulk and strength, these conditions pose a substantial burden to patients as well as to public health.Consequently, there has been considerable interest in a recently described inhibitor of muscle growth, myostatin, or growth/ differentiation factor 8 (GDF-8), which belongs to the transforming growth factor b superfamily of secreted proteins that control the growth and differentiation of tissues throughout the body.The myostatin gene is expressed almost exclusively in cells of skeletal-muscle lineage throughout embryonic development as well as in adult animals and functions as a negative regulator of muscle growth.1,2 Targeted disruption of the myostatin gene in mice doubles skeletal-muscle mass. 1 Conversely, systemic overexpression of the myostatin gene leads to a wasting syndrome characterized by extensive muscle loss.3 In adult animals, myostatin appears to inhibit the activation of satellite cells, which are stem cells resident in skeletal muscle.4,5 The potential relevance of myostatin to the treatment of disease in humans has been suggested by studies involving mdx mice, which carry a mutation in the dystrophin gene and therefore serve as a genetic model of Duchenne's and Becker's muscular dystrophy.6 For example , mdx mice that lacked myostatin were...