RESOURCE FOR RAT GENETIC MODELS OF AEROBIC CAPACITY

描述(由申请人提供)：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。研究人员开发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。经过十代的选择，研究人员记录了低线和高线之间有氧能力的317%的差异。 研究人员请求这些资源来创造、表型和提供这些动物、它们的组织和亲本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，研究人员详细计划为与三个经验丰富的团队的初步合作提供模型：1)William L.Rall和Carl Hansen博士将建立一个冷冻胚胎银行并将其存储在低温储存库中；2)Peter Wagner博士和Noberto Gonzales博士将测量从空气到骨骼肌线粒体的2条运输路径中每一步的电导特性；3)Peter Bouchard博士和Noberto Rankinen博士将使用大规模微阵列技术评估11个组织中的差异信使RNA表达。随后，研究人员提议升级他们的计划，以便在五年内为至少43项主要研究提供低有氧和高有氧大鼠作为资源。[自上次提交以来，调查人员：1)为鼠群隔离屏障区域获得了更多空间，以确保足够的生长；2)升级了哨兵监测计划，大幅加强了对我们群体健康状况的监测。]

DESCRIPTION (Provided by applicant): 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. The investigators 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 ten generations of selection, the investigators recorded a 317% difference in aerobic capacity between the low and high lines. The investigators 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? The investigators present here as an example, detailed plans to provide the models for initial collaborations with three experienced teams: 1) Drs. William L. Rall and Carl Hansen will establish a bank of cryopreserved embryos and store them in a low-temperature repository; 2) Drs. Peter Wagner and Noberto Gonzales will measure the conductance properties of each step of the 2 transport path from the air to the mitochondria of skeletal muscle; and 3) Drs. Peter Bouchard and Noberto Rankinen will evaluate differential messenger RNA expression using large-scale micro-array technology in 11 tissues. Subsequently, the investigators propose to escalate their 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 the investigators have: 1) acquired more space for the rat colony quarantine barrier area to assure adequacy for growth, and 2) upgraded the sentinel surveillance program to substantially increase the monitoring of the health status of our colony.]