Selective Breeding for Insulin Growth Factor 1 in Mice

描述(由申请人提供)：这项建议是一个计划的初始阶段，以产生一个专门建立的动物模型系统，以探索胰岛素样生长因子-1(IGF-1)与衰老过程的相关性。在第一阶段收集的数据将讨论总体战略的可行性，并将为确定后续方案的设计参数提供关键信息。广泛的策略是利用小鼠的选择性育种来产生在血浆IGF-1水平上存在广泛差异的品系。这种通用的方法在许多生物学研究领域都被证明具有巨大的价值。然而，在任何特定的应用中，成功与否取决于 主要取决于被调查性状的遗传性。拟议的研究将评估 胰岛素样生长因子-1水平与胰岛素样生长因子结合蛋白-3、体重、总体脂和体格的候选相关性状 基因异质性亲子代120天龄动物的活动 老鼠。每种表型的遗传力将通过亲子回归、表型 表型之间的相关性将被评估，以及协方差的程度 将通过亲子互协方差分析来估计与遗传的相关性。这些变量的稳定性及其相互关系将通过400日龄时对亲本世代的重新评估来确定。

DESCRIPTION (provided by applicant): This proposal is for the initial phase of a program to generate a purpose-built animal model system for exploring the relevance of insulin-like growth factor-1 (IGF-1) to aging processes. The data collected during this first phase will address the feasibility of the general strategy, and will provide key information for establishing the design parameters for the subsequent program. The broad strategy is to utilize selective breeding in mice to generate lines diverging extensively in plasma levels of IGF-1. This general approach has proved of immense value in many biological research domains. Success in any particular application, however, depends principally upon the heritability of the trait under investigation. The proposed research will assess IGF-1 levels and candidate correlated traits of IGFBP-3, body weight, total body fat, and physical activity in 120-day-old animals of a parent and an offspring generation of genetically heterogeneous mice. Heritabilities of each phenotype will be estimated by parent-offspring regression, phenotypic correlations among the phenotypes will be assessed, and the degree to which the covariance is due to genetic correlation will be estimated by parent-offspring cross-covariance analyses. Stability of these variables and their interrelationships will be determined by reassessment of the parent generation at 400 days of age.