Functional consequences of IGFBP excess-lessons from transgenic mice

The functions of insulin-like growth factor-binding proteins (IGFBPs) have been studied extensively in vitro, revealing IGF-dependent and also IGF-independent effects on cell growth, differentiation, and survival. In contrast, the biological relevance of IGFBPs in vivo is only partially understood. In the past decade, mouse models lacking or overexpressing specific IGFBPs have been generated by transgenic technology. Phenotypic analysis revealed features that are common for most IGFBPs (growth inhibition), but also effects that appear to be specific for some but not all IGFBPs, such as disturbed glucose homeostasis (IGFBP-1 and -3) or impaired fertility (IGFBP-1, -5, and -6). Future systematic comparison of IGFBP functions in transgenic mice will be facilitated by targeted insertion of IGFBP expression vectors and by standardized phenotype assessment. Furthermore, analysis of IGFBP expression in growth-selected mouse lines or pedigrees segregating for growth phenotypes will be important to understand the roles of IGFBPs in multigenic growth regulation.