Abstract
To provide further insight into the function of the IGFBPs, transgenic (Tg) mice which overexpressed IGFBP-1 and IGFBP-3 were generated. In this report we have compared the phenotypic manifestations observed in these Tg mice. The IGFBP-1 Tg mice were significantly smaller at birth, birth weight and gained less weight in the postnatal period. Organ weight was proportionately reduced relative to body weight in most organs. However the brain was markedly smaller in IGFBP-1 Tg mice. Mean plasma levels of Tg-derived IGFBP-1 ranged from 8 to 80 ng ml −1 in the different groups of IGFBP-1 Tg mice. In addition homozygous mice also demonstrated fasting hyperglycemia, impaired glucose tolerance and reduced fecundity. Two of the seven IGFBP-3 founders had measurable levels of hlGFBP-3 in the circulation and were bred to homozygosity. Maximal plasma levels of transgene-derived IGFBP-3 were 72–198 ng ml −1. Transgene expression was detected in the kidney, small intestine and colon by Northern blot analysis. The birth weight, litter size and body weight of IGFBP-3 Tg mice were not significantly different from wild-type mice. However, the spleen, liver and heart of IGFBP-3 Tg mice derived from both founders were significantly heavier compared with organs from wild-type mice. The relative weight of other organs such as the brain, kidney and lungs were similar to wild-type mice. From these data, we conclude that over expression of IGFBP-1 results in inhibition of IGF action and in profound impairment of brain development, modest inhibition of fetal and postnatal growth and inhibition of the metabolic effects of the IGFs. In contrast, modest overexpression of hlGFBP-3 has little effect other than some selective organomegaly.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.