Do lamin A/C and emerin mutations in satellite cells contribute to Emery-Driefuss muscular dystrophy?

卫星细胞中的核纤层蛋白 A/C 和 emerin 突变是否会导致 Emery-Driefuss 肌营养不良症？

• 批准号: G0700307/1
• 负责人: Peter Zammit
• 金额: $ 51.5万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0700307%2F1
• 关键词: Do; lamin; emerin; mutations; satellite

Muscle is made of thousands of muscle fibres, which are repaired and regenerated by muscle stem cells called satellite cells. Muscular dystrophies are a group of inherited disorders that are characterised by progressive muscle weakness and degeneration. Since muscle is responsible for movement, its gradual loss in muscular dystrophies can severely affect the quality of life of a patient, and in some disorders, drastically shorten their lifespan. Compromised satellite cell function is thought to contribute to loss of muscle in some of these conditions, including Emery-Dreifuss muscular dystrophy (EDMD). It has been shown that EDMD is caused by problems in genes that make proteins involved in maintaining a healthy nucleus. We intend to examine satellite cells from patients suffering from EDMD to understand how these mutated proteins affected their function and so muscle repair. We will also use mouse models of the disease to study satellite cell biology. Findings on mouse satellite cells should be broadly applicable to man. Theoretically, manipulation of satellite cells could both augment and prolong muscle function in people with muscular dystrophy, which also has the advantage of maintaining a muscle environment still capable of responding to other forms of therapy.

肌肉由数以千计的肌肉纤维组成，这些纤维由称为卫星细胞的肌肉干细胞修复和再生。肌营养不良症是一组遗传性疾病，以进行性肌肉无力和退化为特征。由于肌肉负责运动，肌肉营养不良症中肌肉的逐渐丧失会严重影响患者的生活质量，在某些疾病中，会极大地缩短他们的寿命。卫星细胞功能受损被认为是其中一些情况下肌肉丧失的原因，包括Emery-Dreifuss肌营养不良症(EDMD)。已经证明，EDMD是由基因问题引起的，这些基因使蛋白质参与维持健康的细胞核。我们打算检查患有EDMD的患者的卫星细胞，以了解这些突变的蛋白质如何影响它们的功能，从而影响肌肉修复。我们还将使用这种疾病的小鼠模型来研究卫星细胞生物学。对小鼠卫星细胞的研究结果应该广泛适用于人类。从理论上讲，操纵卫星细胞既可以增强和延长肌营养不良症患者的肌肉功能，也有保持仍能对其他形式的治疗产生反应的肌肉环境的优势。