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：动物存储库和肌肉力量的测量，David D. Thomas，博士 该核心的目的是提供一个动物存储库，专注于肌肉疾病的小鼠模型，并提供 提供设施和专业知识，以测量从活体动物到单一级别的各个级别的肌肉力量 分子。肌肉的主要功能是力产生。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 对治疗的反应，我们将表征实验受试者的力和分子结构，包括 所有MD中心研究人员都可以使用且负担得起的动物模型。这些设施将提供 MD中心几乎所有项目的重要资源，并将包括一个测试设施和 方法对所有肌肉研究人员都很有价值。具体目的是为以下设施建立设施： AIM 1：维护肌肉营养不良和其他肌病的选定小鼠模型的育种对，因此 MD中心研究人员可以更有效地对不同模型进行协作研究。 目标2：测量人类，小鼠和其他动物体内刺激的肌肉力量，直接激活该肌肉 神经神经来消除中枢神经系统和全身作用。 目标3：从整个小鼠肌肉和纤维束的体外测量完整肌肉的力量 通过电气或化学刺激进行活检，测量抽搐和甲烷的作用，以及放松的速度和 激活。 目标4：在体外测量皮肤纤维的力，以分别评估肌膜与电化学 功能。 AIM 5：使用（a）揭示分子的（a）的Specrrososcic探针在分子水平上测量力 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），它直接测量单分子的机械性能。 这些鼠标模型和技术功能中的大多数目前都在明尼苏达大学运作 但是由于技术复杂性和单独的资金机制，目前每个鼠标模型和技术都是 对于有限数量的调查人员，可以在实际级别上访问，目前的费用限制了 这些动物和技术合并为合作项目。通过中央组织的 资助的核心，我们将使所有MD中心调查员都可以访问和负担得起，从而大大增加了 MD中心研究的连贯性和有效性。