GENETIC MODEL OF ENDURANCE EXERCISE IN RATS

描述（申请人摘要）：有氧运动能力是一种表型， 具有重要的生物学和临床意义。我们的长期目标是 开发大鼠有氧运动能力的遗传模型，可用于 确定基因之间的差异负责低和高的能力。到 为了实现这一目标，我们开始了有氧跑步机的分歧选择育种 在192只N/Nih大鼠的建立者群体中的跑步能力。十三交配 表现出实质性育种价值的配对是从 创始人人口在低和高极端的有氧能力。三 几代的选择性育种产生了117%的差异， 有氧跑高低选线成绩 容量本工作的具体目标是：1。继续选择 有氧耐力育种能力，直到选择的反应， 这种特性在低和高线中减弱。选择平台将 在操作上被定义为当对选择的反应不显著时， 连续三代都不同。2.创建对比鲜明的近交系 低和高有氧运动能力的大鼠。为了实现这一目标，13个家庭， 选择的低和高品系将是严格的兄弟姐妹（全同胞） 交配了20代或更多代。最佳有氧运动员的选拔将是 一直延续到近亲繁殖3.继续选择性繁殖 在特定目标1中创造的20代或更多代的分歧系， 表观平台选择性繁殖将继续过去的高原两个 原因：a）确保达到选择限制，以及B） 作为起源额外的近交家庭的来源。到2000年， 人类基因组的转录区域将被测序。 虽然这代表着一项重大成就，但功能只占一小部分 基因组的信息将被知晓。下一步将是使用遗传模型， 将基因与功能联系起来。鉴定负责 低和高有氧运动能力之间的差异将形成一个更广泛的 为了解健康的遗传起源奠定基础，并为人类健康开辟新的道路。 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.