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Institute of Molecular Animal Breeding, Gene Center, D-81377 Munich, Germany
1Correspondence: Institute of Molecular Animal Breeding, Gene Center, Feodor-Lynen-Strasse 25, D-81377 Munich, Germany. E-mail: ewolf{at}lmb.uni-muenchen.de
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 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.—Schneider, M. R., Lahm, H., Wu, M., Hoeflich, A., Wolf, E. Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins.
Key Words: IGFBP • insulin-like growth factors • transgenic mice • overexpression • knockout
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