Dystrophic Mouse Colony and Force Assessment

营养不良小鼠群体和力评估

• 批准号: 8323821
• 负责人: David D Thomas
• 金额: $ 13.37万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8323821
• 关键词: Actins; Action Potentials; Adhalin; Animal Model; Animals; Appearance; Binding; Biopsy; Breeding; Bypass; Cardiomyopathies; Chemicals; Complement; Coupling; Disease; Disease Progression; Doctor of Philosophy; Dystrophin; Effectiveness; Electrodes; Electron Spin Resonance Spectroscopy; Elements; Fiber; Filament; Functional disorder; Funding; Funding Mechanisms; Generations; Goals; Head; Human; In Vitro; Individual; Institutional Review Boards; Joints; Knock-out; Knockout Mice; Laboratories; Lasers; Life; Measurement; Measures; Mechanics; Methodology; Methods; Microfilaments; Minnesota; Modeling; Molecular; Molecular Structure; Motor; Mus; Muscle; Muscle Fibers; Muscle function; Muscular Dystrophies; Myopathy; Myosin ATPase; Myotonic Dystrophy; Nerve; Neural Conduction; Neuraxis; Property; Protocols documentation; Relaxation; Research; Research Methodology; Research Personnel; Resources; Site; Skin; Specimen; Spin Labels; Stimulus; Techniques; Testing; Time; Torque; Troponin; Universities; Utrophin; awake; biceps brachii muscle; in vivo; laser tweezer; mouse model; muscular dystrophy mouse model; mutant; overexpression; pressure; repository; response; single molecule; tibialis anterior muscle

Research Core C: Animal Repository and Measurement of Muscle Force, David D. Thomas, PhD The purpose of this core is to provide an animal repository, focused on mouse models of muscle disease, and to provide facilities and expertise for the measurement of muscle force at all levels from living animals to single molecules. The primary function of muscle is force generation. To further characterize the pathophysiology of muscle disease and establish accurate methods for determining the time course of disease progression and response to treatment, we will characterize force and molecular structure in experimental subjects, including animal models that will be available and affordable to all MD Center researchers. These facilities will provide important resources for virtually all projects of the MD center, and will comprise a testing facility and methodology valuable to all muscle investigators. Specific aims are to establish facilities for the following: Aim 1: Maintain breeding pairs of selected mouse models of muscular dystrophy and other myopathies, so MD Center investigators can more effectively perform collaborative studies of the different models. Aim 2: Measure stimulated muscle force in vivo in humans, mice, and other animals, directly activating the innervating nerve to obviate central nervous system and systemic effects. Aim 3: Measure force of intact muscle in vitro from whole mouse muscles and bundles of fibers from human biopsies by electrical or chemical stimuli, to measure twitch and tetanic force, and rates of relaxation and activation. Aim 4: Measure force of skinned fibers in vitro, to assess myofilaments separately from electrochemical function. Aim 5: Measure force at the molecular level, using either (a) specrroscopic probes that reveal molecular structural and dynamic states that correspond to force generation or mechanical strength, and (b) laser tweezers (laser traps), which measures directly the mechanical properties of single molecules. Most of these mouse models and technical capabilities are currently operational at the University of Minnesota, but due to technical complexity and separate funding mechanisms, each mouse model and technique is currently accessible at a practical level for a limited number of investigators, and expenses currently limit the extent to which these animals and techniques are combined in collaborative projects. Through a centrally organized and funded Core, we will make them accessible and affordable to all MD Center investigators, greatly increasing the coherence and effectiveness of MD Center research.

研究核心C：动物肌肉力量的储存和测量，大卫D。托马斯，博士 这个核心的目的是提供一个动物库，专注于肌肉疾病的小鼠模型， 提供设施和专业知识，用于测量从活体动物到单个 分子。肌肉的主要功能是产生力量。为了进一步表征 肌肉疾病，并建立准确的方法来确定疾病进展的时间过程， 治疗反应，我们将在实验对象中表征力和分子结构，包括 动物模型，将提供和负担得起的所有医学博士中心的研究人员。这些设施将提供 MD中心几乎所有项目的重要资源，将包括一个测试设施， 对所有肌肉研究者都有价值的方法。具体目标是为以下方面建立设施： 目的1：维持选定的肌肉萎缩症和其他肌病小鼠模型的繁殖对， MD中心的研究人员可以更有效地进行不同模型的协作研究。 目的2：测量人类、小鼠和其他动物体内的刺激肌肉力量，直接激活肌肉。 影响中枢神经系统和全身效应。 目的3：测量小鼠完整肌肉和人肌纤维束的体外完整肌肉的力 通过电刺激或化学刺激进行活检，以测量抽搐和强直力，以及松弛率， activation. 目的4：测量离体皮肤纤维的力，以分别评估肌丝和电化学 功能 目标5：在分子水平上测量力，使用（a）光谱探针， 对应于力产生或机械强度的结构和动态状态，以及（B）激光镊子 （激光陷阱），其直接测量单个分子的机械性质。 大多数这些小鼠模型和技术能力目前在明尼苏达大学运行， 但由于技术的复杂性和单独的资金机制，每种小鼠模型和技术目前都是 在实践层面上，有限数量的调查人员可以使用，目前的费用限制了 这些动物和技术在合作项目中结合起来。通过一个集中组织和 资助的核心，我们将使他们访问和负担得起的所有医学博士中心的研究人员，大大增加了 MD中心研究的一致性和有效性。