RESOURCE FOR RAT GENETIC MODELS OF AEROBIC CAPACITY

超出所提供的空间。细胞利用氧作为电子受体（有氧代谢）进行能量转移的能力决定了我们所有组织的生物学水平的一个主要方面。我们开发了低和高内在（未经训练）有氧能力的大鼠模型，并对这些大鼠的样本进行了大量的研究。这些模型是在1996年从168只N:NIH大鼠开始的。采用不同的人工选择育种来创建低线和高线，以对比有氧跑步机的运行能力。经过10代的选育，低系和高系的有氧能力差异达317%。我们要求资源来创建，表型，并提供这些动物，他们的组织，亲代DNA供他人研究。23名研究人员要求使用这些模型来回答以前无法探索的问题，例如：1)哪些表型与内在（即未经训练的）有氧能力完全相关？2)差异表达分析是否会揭示以前未被怀疑的促进内在有氧能力的途径？3)有氧能力与健康之间的正相关关系在多大程度上来自于内在能力而不是训练能力？4)哪些与健康相关的特征与内在能力相关，如长寿或对糖尿病、高血压、心脏病、肥胖、癌症或传染病的抵抗力？我们在这里举个例子，详细的计划为我们与三个经验丰富的团队的初始合作提供模型：瑞尔和汉森将建立一个冷冻胚胎库，并将它们储存在低温储存库中。2) Drs。Wagner和Gonzales将测量从空气到骨骼肌线粒体的02传输路径的每一步的电导特性。3) Drs。Bouchard和Rankinen将利用大规模微阵列技术评估11种组织中的差异信使RNA表达。随后，我们建议升级我们的计划，以便在五年内提供低氧和高氧大鼠作为至少43项主要研究的资源。[自上次提交以来，我们已经：1)为我们的鼠群隔离隔离区获得了更多的空间，以确保足够的生长，以及2)升级了我们的哨点监测计划，以大大增加对我们的鼠群健康状况的监测。]网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. The ability of cells to utilize oxygen as an electron acceptor (aerobic metabolism) for energy transfer defines a major aspect of our biology at all levels of organization. We developed rat models for low and high intrinsic (untrained) aerobic capacity and have had numerous requests for samples of these rats to study. These models were started in 1996 from a founder population of 168 N:NIH rats. Divergent artificial selective breeding was applied to create low and high lines that contrast for aerobic treadmill running capacity. After 10 generations of selection we recorded a 317% difference in aerobic capacity between the low and high lines. We request the resources to create, phenotype, and provide these animals, their tissues, and parental DNA for others to study. Appended to this grant are requests from 23 investigators to use these models to answer previously unexplorable questions such as: 1) What phenotypes are associated exclusively with intrinsic (i.e., untrained) aerobic capacity? 2) Will differential expression analysis reveal previously unsuspected pathways that contribute to intrinsic aerobic capacity? 3) To what extent does the positive association between aerobic capacity and health accrue from intrinsic capacity relative to trained capacity? 4) What health-related traits correlate with intrinsic capacity, such as longevity or resistance to diabetes mellitus, hypertension, heart disease, obesity, cancer, or infective agents? We present here as an example, detailed plans to provide our models for initial collaborations with three experienced teams: 1) Drs. Rail and Hansen will establish a bank of cryopreserved embryos and store them in a low-temperature repository. 2) Drs. Wagner and Gonzales will measure the conductance properties of each step of the 02 transport path from the air to the mitochondria of skeletal muscle. 3) Drs. Bouchard and Rankinen will evaluate differential messenger RNA expression using large-scale micro-array technology in 11 tissues. Subsequently, we propose to escalate our plan in order to provide low and high aerobic rats as a resource for a minimum of 43 major studies over five years. [Since last submission we have: 1) acquired more space for our rat colony quarantine barrier area to assure adequacy for growth, and 2) upgraded our sentinel surveillance program to substantially increase the monitoring of the health status of our colony.] PERFORMANCE SITE ========================================Section End===========================================