Selective Breeding for Insulin Growth Factor 1 in Mice

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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.