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各级组织中的一个主要方面。 研究人员开发了低和高内在（未经训练的）有氧能力的大鼠模型，并多次要求这些大鼠的样本进行研究。 这些模型于1996年从168只N：NIH大鼠的建立者群体开始。 采用不同的人工选择育种方法，建立了有氧跑台运动能力的高、低品系。经过10代的选择，研究人员记录了低和高品系之间有氧能力的317%差异。 研究人员要求资源来创建，表型，并提供这些动物，它们的组织和亲本DNA供其他人研究。 23名研究人员要求使用这些模型来回答以前无法探索的问题，如：1）什么表型与内在（即，未经训练）有氧能力？ 2)差异表达分析是否能揭示以前未被怀疑的导致内在有氧能力的途径？ 3)有氧能力和健康之间的正相关在多大程度上是由内在能力相对于训练能力产生的？ 4)什么样的健康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、癌症或感染因子的抵抗力？ 研究人员在这里提出了一个例子，详细的计划，以提供与三个经验丰富的团队初步合作的模型：1）威廉L。Rall和Carl汉森将建立一个冷冻胚胎库，并将其储存在低温储存库中; 2）Peter瓦格纳和Noberto冈萨雷斯博士将测量从空气到骨骼肌线粒体的2个运输路径的每一步的电导特性; Peter Bouchard和Noberto Rankinen博士将使用大规模微阵列技术在11种组织中评估差异信使RNA表达。随后，研究人员建议升级他们的计划，以便在五年内提供低有氧和高有氧大鼠作为至少43项主要研究的资源。 [自上次提交以来，研究者已：1）为大鼠种群隔离屏障区域获得更多空间，以确保足够的生长，2）升级哨兵监测计划，以大幅增加对我们种群健康状况的监测。]

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.]