RESOURCE FOR RAT GENETIC MODELS OF AEROBIC CAPACITY

超出提供的空间。细胞利用氧作为电子受体(有氧代谢)进行能量转移的能力定义了我们生物学在所有组织水平上的一个主要方面。我们建立了低固有有氧能力和高固有有氧能力的大鼠模型，并要求对这些大鼠的样本进行研究。这些模型始于1996年，由168只N：NIH大鼠组成的创始种群。发散的人工选择育种被用来创造有氧跑步机运行能力对比的低线和高线。经过10个世代的选择，我们记录到低和高品系的有氧能力存在317%的差异。我们请求资源来创造，表型，并提供这些动物，他们的组织，和父母的DNA，供其他人研究。23名研究人员请求使用这些模型来回答以前无法探索的问题，例如：1)哪些表型仅与内在(即，未经训练的)有氧能力有关？2)差异表达分析是否会揭示与内在有氧能力有关的先前未知的途径？3)相对于训练能力，有氧能力与健康之间的正相关程度如何？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、癌症或感染性物质的抵抗力？作为一个例子，我们在这里提供了详细的计划，为我们与三个经验丰富的团队的初步合作提供模型：1)Rail博士和Hansen博士将建立一个冷冻胚胎储存库，并将它们存储在低温储存库中。2)瓦格纳和冈萨雷斯博士将测量从空气到骨骼肌线粒体的02运输路径每一步的电导特性。3)Bouchard和Rankinen博士将利用大规模微阵列技术在11个组织中评估差异信使RNA的表达。随后，我们建议升级我们的计划，以便在五年内提供低有氧和高有氧大鼠作为资源，用于至少43项主要研究。[自上次提交以来，我们已经：1)为我们的鼠群隔离屏障区域获得了更多的空间，以确保足够的生长，以及2)升级了我们的哨兵监测计划，以大幅加强对我们群体健康状况的监测。]表演网站========================================Section End===========================================

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===========================================