MYOGENIC FACTORS: MUSCLE MATURATION AND REGENERATION

生肌因素：肌肉成熟和再生

• 批准号: 6652674
• 负责人: Marcia R. Ontell
• 金额: $ 27.3万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6652674
• 关键词: cadherins; cell differentiation; cell proliferation; gel electrophoresis; gene expression; immunocytochemistry; laboratory mouse; muscle satellite cell; muscle transplantation; myogenesis; polymerase chain reaction

DESCRIPTION (appended verbatim from investigator's abstract): Myf 5 and MyoD play critical roles in the specification and/or maintenance of muscle progenitor cells during development. While "knock out" mice provide a valuable tool for determining which functions of these factors are unique and the extent to which they might overlap, that Myf 5 null mice die at birth has limited the study of the maturation and regeneration of Myf 5 null muscles. By transplanting newborn Myf 5 null extensor digitorum longus (EDL) muscles into the bed of normal hosts (where these muscle regenerate and become innervated), we can compare these processes in Myf 5 and MyoD null mice. MyoD null muscles exhibits a regeneration deficit involving an inhibition of its satellite cells ability to undergo terminal differentiation; whereas, it is suggested that Myf 5 null myoblasts undergo precocious differentiation. Comparative studies of Myf 5 null, MyoD null and wild type muscle regeneration will be carried out with EM and morphometric analyses. The effect of the absence of Myf 5 on the number of satellite cell, satellite cell activation, proliferation and terminal differentiation will be assessed in regenerating muscle and in vitro. The effects of the absence of Myf 5 on muscle gene expression (e.g., genes encoding the MRFs, M cadhedrin, desmin, c met tyrosine kinase, etc.) in regenerating muscles and in cultures of myosatellite cells will be evaluated with competitive PCR and immunohistochemistry. Comparisons will be made with similar studies of normal and MyoD null regenerating muscle (Sabourin et al., 1999). The effect of the absence of Myf 5 on muscle phenotype will be evaluated with immunohistochemistry and gel electrophoresis. Muscle diseases are characterized by degeneration regeneration, with the regenerative effort being insufficient to keep pace with degeneration. These studies should provide clues to how it may be possible to increase muscle's regenerative response.

描述(逐字摘自调查人员摘要)：MyF5和MyoD 在肌肉的规范和/或维护中扮演关键角色 发育过程中的祖细胞。虽然“敲除”的老鼠提供了有价值的 用于确定这些因素的哪些功能是唯一的及其程度的工具 它们可能重叠在一起，Myf5无效小鼠在出生时死亡限制了 Myf5缺损肌的成熟与再生研究。通过 新生MYF5缺失指长伸肌移植入 正常宿主的床(这些肌肉在这里再生并得到神经支配)， 我们可以比较Myf5和MyoD基因缺失小鼠的这些过程。MyoD缺陷肌 表现出再生缺陷，包括对其卫星细胞的抑制 进行末端分化的能力；然而，有人认为Myf 5空成肌细胞经性早熟分化。MYF的比较研究 5 Null、MyoD Null和野生型肌肉再生将使用EM进行 和形态计量分析。MYF5缺失对血吸虫数量的影响 卫星细胞、卫星细胞的激活、增殖和终末 分化将在再生肌肉和体外进行评估。这个 MyF5缺失对肌肉基因表达(如编码基因)的影响 MRF、M钙粘蛋白、结蛋白、c-Met酪氨酸激酶等。在再生中 肌肉和培养的肌卫星细胞将用 竞争性聚合酶链式反应和免疫组织化学。将与类似的 对正常和MyoD零再生肌肉的研究(Sabourin等人，1999年)。 Myf5缺失对肌肉表型的影响将通过以下方法进行评估 免疫组织化学和凝胶电泳法。肌肉疾病的特点是 通过退化再生，再生的努力不够 以跟上退化的步伐。这些研究应该提供线索，说明它是如何 可能会增加肌肉的再生反应。