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lüll Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins Schneider MR; Lahm H; Wu M; Hoeflich A; Wolf EFASEB J 2000[Apr]; 14 (5): 629-40The 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 competition they can affect cell growth. In addition, IGF-independent regulatory 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 were a common feature of IGFBP-1 transgenic models. Individual strains showed alterations in glucose homeostasis, reproductive performance, and a reduction 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 caused an altered involution after pregnancy in this organ. Tissue-specific overexpression of IGFBP-4 resulted in hypoplasia and reduced weight of smooth muscle-rich tissues such as bladder, aorta, and stomach. This review summarizes the current knowledge about the actions of IGFBPs in vivo based on the presently established transgenic mice.|Animals[MESH]|Female[MESH]|Gene Expression[MESH]|Glucose/metabolism[MESH]|Growth Disorders/genetics[MESH]|Homeostasis[MESH]|Insulin-Like Growth Factor Binding Proteins/*genetics/*physiology[MESH]|Male[MESH]|Mice[MESH]|Mice, Knockout[MESH]|Mice, Transgenic[MESH]|Phenotype[MESH]|Pregnancy[MESH]|Reproduction/genetics[MESH] |