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 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
MR
Institute of Molecular Animal Breeding, Gene Center, D-81377 Munich, Germany.
Lahm
H
H
Wu
M
M
Hoeflich
A
A
Wolf
E
E
D000818:Animals; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006130:Growth Disorders / Q000235:genetics; D006706:Homeostasis; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics* / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011247:Pregnancy; D012098:Reproduction / Q000235:genetics
D018969:Insulin-Like Growth Factor Binding Proteins; D005947:Glucose