Dystrophic Mouse Colony and Force Assessment

营养不良小鼠群体和力评估

基本信息

批准号：
8508075
负责人：
David D Thomas
金额：
$ 23.26万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2014-12-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8508075
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

项目摘要

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测量，David D. Thomas 博士该核心的目的是提供一个动物资源库，重点关注肌肉疾病的小鼠模型，并提供用于测量从活体动物到单个个体的各个级别的肌肉力量的设施和专业知识分子。肌肉的主要功能是产生力量。为了进一步表征病理生理学肌肉疾病并建立准确的方法来确定疾病进展的时间过程和对治疗的反应，我们将表征实验对象的力和分子结构，包括所有 MD 中心研究人员都可以获得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，并将包括测试设施和对所有肌肉研究人员有价值的方法。具体目标是为以下目的建立设施：目标 1：维持选定的肌营养不良症和其他肌病小鼠模型的繁殖对，以便 MD 中心的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受刺激的肌肉力量，直接激活支配神经以避免中枢神经系统和全身效应。目标 3：在体外测量小鼠完整肌肉和人体纤维束的完整肌肉力量通过电或化学刺激进行活组织检查，以测量抽搐和强直力以及松弛和放松的速率激活。目标 4：在体外测量带皮纤维的力，以独立于电化学评估肌丝功能。目标 5：使用 (a) 揭示分子水平的光谱探针测量分子水平的力与力产生或机械强度相对应的结构和动态状态，以及（b）激光镊子（激光陷阱），直接测量单分子的机械性能。大多数这些小鼠模型和技术能力目前已在明尼苏达大学投入使用，但由于技术复杂性和独立的资助机制，每种小鼠模型和技术目前都处于对于有限数量的研究人员来说，可以在实际水平上使用，并且目前的费用限制了其程度这些动物和技术在合作项目中相结合。通过集中组织和资助的核心，我们将使所有 MD 中心研究人员可以使用和负担得起它们，从而大大增加 MD 中心研究的连贯性和有效性。