Genetic Model of Endurance Exercise in Rats

描述(申请人摘要)：有氧运动能力是 基础生物学和临床重要性。我们的长期目标是 建立大鼠有氧运动能力的遗传模型，可用于 找出导致低容量和高容量差异的基因。至 为了实现这一目标，我们开始了有氧跑步机的发散选育 在192只N/NIH大鼠的创始种群中的运行能力。十三次交配 表现出显著育种价值的配对选自 创业者群体处于有氧能力的低、高两个极端。三 几代人的选择繁殖产生了117%的差异 低选线和高选线在有氧跑中的表现 容量。这项工作的具体目标是：1.继续有选择地 有氧耐力的选育直到对选择的反应 这一特征在低线和高线上都有所减弱。选拔平台期将 在操作上被定义为对选择的反应不显著 连续三代都不同。2.创造对比鲜明的自交系 低有氧运动能力和高有氧运动能力大鼠。为了做到这一点，来自中国的13个家庭 低选系和高选系将严格采用兄妹关系(全同胞)。 交配了20代或更多代。最佳有氧表演者的评选将是 在整个近亲交配过程中一直持续。3.继续选育 在特定目标1中创建了20代或更多世代的发散线条 明显处于平台期。选择育种将在高原上继续进行两个人 理由：a)确保已达到选拔限制，b)服务 作为产生更多近亲交配家庭的来源。到2000年，大多数 人类基因组转录区域的一部分将被测序。 虽然这是一项重大成就，但只有一小部分的功能 基因组的部分就会知道了。下一步将是使用遗传模型来 将基因与功能联系起来。鉴定--对致病基因的鉴定 低有氧运动能力和高有氧运动能力之间的差异将形成更广泛的 为理解健康的基因起源奠定了基础，并导致了 疾病的预防和治疗。

DESCRIPTION (Applicant's abstract): Aerobic exercise capacity is a phenotype of fundamental biological and clinical importance. Our long-term goal is to develop genetic models of aerobic exercise capacity in rats that can be used to identify genes responsible for differences between low and high capacity. To achieve this goal we started divergent selective breeding for aerobic treadmill running capacity in a founder population of 192 N/Nih rats. Thirteen mating pairs that demonstrated substantial breeding values were selected from the founder population at the low and high extremes of aerobic capacity. Three generations of selective breeding produced a 117 percent difference in performance between the low and high selected lines for aerobic running capacity. The Specific Aims of this work are to: 1. Continue the selective breeding for aerobic endurance capacity until the response to selection for this trait is diminished in the low and high lines. The selection plateau will be operationally defined as when the response to selection is not significantly different for three successive generations. 2. Create contrasting inbred lines of low and high aerobic performance rats. To accomplish this, 13 families from the low and high selected lines will be strictly brother-sister (full-sib) mated for 20 or more generations. Selection for best aerobic performers will be continued throughout the inbreeding. 3. Continue selective breeding of the divergent lines created in specific aim 1 for 20 or more generations past the apparent plateau. Selective breeding will be continued past the plateau for two reasons: a) to assure that a selection limit has been reached, and b) to serve as a source for originating additional inbred families. By the year 2000 most of the transcribed regions of the human genome will have been sequenced. Although this represents a major achievement, the function of only a small part of the genome will be known. The next step will be the use of genetic models to connect genes with function. Identification-of genes responsible for the differences between low and high aerobic exercise capacity would form a broader base for understanding the genetic origins of health, and lead to new paths for the prevention and treatment of disease.