A myoutube-specific deletion model for sarcopenia

肌肉减少症的肌管特异性缺失模型

• 批准号: 8454456
• 负责人: PAUL Taylor MARTIN
• 金额: $ 15.48万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-05 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8454456
• 关键词: 3 year old; Actins; Adult; Affect; Age; Age-Months; Aging; Animal Model; Animals; Binding; Biological; Biology; Cells; Development; EGF gene; Elderly; Environment; Fracture; Fucosyltransferase 1; Growth; Health; Human; Intramuscular; Ligand Binding; Ligands; Longevity; Mediator of activation protein; Mitotic Activity; Modeling; Molecular; Mus; Muscle; Muscle satellite cell; Muscular Dystrophies; Myopathy; Phenotype; Play; Process; Proteins; Public Health; Receptor Signaling; Rodent Model; Role; Signal Transduction; Skeletal Muscle; Testing; Therapeutic; alpha Actin; cell type; extracellular; frailty; glycosylation; glycosyltransferase; knock-down; mdx mouse; mouse model; muscle aging; muscle form; muscle regeneration; muscle strength; notch protein; overexpression; premature; receptor; regenerative; sarcopenia; satellite cell; skeletal

DESCRIPTION (provided by applicant): During aging, humans can lose up to one third of their skeletal muscle mass. Such aging-associated muscle loss is referred to as sarcopenia. Sarcopenia is a contributing factor to a number of serious public health issues, including bone fractures, loss of ambulation and overall frailty in the elderly. While some advances have been made in understanding sarcopenia using animal models, rodent models most commonly used to study this aspect of muscle biology require aging animals 2-3 years, an age that is at or beyond the animal's normal lifespan. Here we describe a new mouse model for sarcopenia where most relevant hallmarks, including loss of muscle mass, size and strength are evident by 6 months of age. These phenotypes result from myofiber-specific deletion of Pofut1 (Skeletal alpha actin (Sk)-CreTgPofut1loxP), or Protein O-fucosyltransferase 1. Pofut1 is an essential glycosyltransferase that is required for ligands to bind to Notch receptors. Notch receptors and Notch ligands have been shown to be important mediators of the biology underlying the reduced mitotic activity of satellite cells, the principal regenerative pool of muscle stem cells, with age This proposal will provide the first demonstration that Notch activity in the skeletal myofiber als contributes to muscle aging and will allow the specific study of the role of myofiber Notch receptors in muscle regeneration, muscle growth and muscle disease.

描述（由申请人提供）：在衰老期间，人类可能会损失多达三分之一的骨骼肌质量。这种与衰老相关的肌肉损失称为肌肉减少症。肌肉减少症是导致许多严重的公共卫生问题的一个因素，包括骨折，流动损失和老年人的整体脆弱。尽管使用动物模型在理解肌肉减少症方面已取得了一些进步，但啮齿动物模型最常用于研究肌肉生物学的这一方面需要2-3岁的衰老动物，而该年龄属于动物正常寿命。在这里，我们描述了一种用于肌肉减少症的新小鼠模型，其中最相关的标志（包括肌肉质量，大小和力量的损失）在6个月大时就显而易见。这些表型是由pofut1（骨骼α肌动蛋白（SK）-CretgPofut1loXP）或蛋白O-羟基转移酶1。POFUT1的肌纤维特异性缺失引起的。POFUT1是与Notch受体结合所必需的必不可少的糖基转移酶。已经证明Notch受体和缺口配体是卫星细胞降低有丝分裂活性的生物学的重要介体，肌肉干细胞的主要再生池，随着年龄的增长，该建议将提供首次证明，即在骨骼肌纤维中的骨骼肌肉菌Als中有助于肌肉的疾病和脑部的腔unser unser unser unsermuls use的作用，从而提供了肌肉疾病的生长。