Selective Breeding for Insulin Growth Factor 1 in Mice

描述（由申请人提供）：该提案是针对一项计划的初始阶段，该计划旨在生成一个专门构建的动物模型系统，用于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说明总体战略的可行性，并将为建立后续计划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IGF-1的血浆水平上广泛发散的品系。这种通用方法在许多生物学研究领域已被证明具有巨大的价值。然而，任何特定应用的成功都取决于 主要取决于所研究性状的遗传力。该研究将评估 IGF-1水平与IGFBP-3、体重、总体脂和体格检查的候选相关性状 活性在120日龄动物的父母和后代的遗传异质性 小鼠每种表型的遗传力将通过亲本-后代回归、表型 将评估表型之间的相关性，以及协方差的程度 遗传相关性将通过亲本-后代交叉协方差分析来估计。 这些变量的稳定性及其相互关系将通过在400日龄时重新评估亲代来确定。

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.