Investigating the role of beta-1 integrin in regulating the adult satellite cell

描述（由申请人提供）：哺乳动物的肌肉组织为运动提供机械力。该系统在整个生命周期中经历重塑，并显示出从肌肉干细胞（称为卫星细胞）库再生的非凡能力。然而， 这些细胞是如何保持静止状态和再生能力的，在很大程度上是不确定的。我建议通过使用Pax 7-Cre-ERT 2融合基因来确定b1-整联蛋白在这些过程中的作用（Pax 7 CE等位基因）用于他莫昔芬（tmx）诱导的b1-整联蛋白条件等位基因的基因失活目的1：β 1-整联蛋白在静止卫星细胞中的功能：我将在正常稳态下检查b1整合素失活的卫星细胞， 评估：1）静止卫星细胞需要β 1整合素吗？2)b1整合素的缺失是否影响 卫星细胞与细胞外基质的粘附？目标二：整合素β 1在卫星细胞活化中的作用：我将用损伤模型进一步探讨：1）整合素β 1缺失的卫星细胞能否维持肌肉再生？2)整合素缺失的卫星细胞会被激活并增殖吗？

DESCRIPTION (provided by applicant): The mammalian musculature provides mechanical force for locomotion. This system undergoes remodeling throughout lifetime and displays remarkable ability to regenerate from reservoirs of muscle stem cells, called satellite cells. Yet, how these cells are maintained, both in their quiescent state as well as in their regenerative capacity, is largely undefined. I propose to define the role of b1-integrin in these processes by using a Pax7-Cre-ERT2 fusion gene (the Pax7CE allele) for tamoxifen (tmx) inducible gene inactivation of a conditional allele of b1-integrin (b1-integrinflox), coupled with lineage tracingto address the questions outlined in the aims below: Aim 1: Function of b1-integrin in the quiescent satellite cell: I will examine b1- integrin inactivated satellite cells under normal homeostasis to assess: 1) Do quiescent satellite cells require b1-integrin? 2) Does the loss of b1-integrin affect adhesion of the satellite cell to the extracellular matrix? Aim 2: Function of b1-integrin in satelite cell activation: I will use injury models to further ask: 1) Can b1-integrin null satellite cells sstain muscle regeneration? 2) Do b1- integrin null satellite cells become activated and proliferate?