Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins

The insulin-like growth factor-binding proteins (IGFBPs) comprise a family of six related peptides that interact with high affinity with IGFs. IGFBPs compete with IGF receptors for IGF binding, and as a consequence of this co mpetition they can affect cell growth. In addition, IGF-independent regulat ory mechanisms of IGFBPs have been described. Despite their common property to interact with IGFs every IGFBP is expressed in a tightly regulated time - and tissue-specific manner suggesting that each protein may have its own distinct functions. Several transgenic mouse models overexpressing IGFBP-1, -2, -3, or -4 were developed in the past few years. Brain abnormalities we re a common feature of IGFBP-1 transgenic models. Individual strains showed alterations in glucose homeostasis, reproductive performance, and a reduct ion of somatic growth as the most prominent phenotypes. The latter was also the main effect observed in IGFBP-2 transgenic mice. The overexpression of IGFBP-3 under the control of an ubiquitous promoter resulted in selective organomegaly, whereas mammary gland-targeted expression of this protein cau sed an altered involution after pregnancy in this organ. Tissue-specific ov erexpression of IGFBP-4 resulted in hypoplasia and reduced weight of smooth muscle-rich tissues such as bladder, aorta, and stomach. This review summa rizes the current knowledge about the actions of IGFBPs in vivo based on th e presently established transgenic mice.-Schneider, hi. R., Lahm, H., Wu, M ., Hoeflich, A., Wolf, E. Transgenic mouse models for studying the function s of insulin-like growth factor-binding proteins.